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Prof. Dr. Mustafa Özdoğan · Medical Oncologist

What Does the Ki-67 Value in a Pathology Report Mean? What Does a High Ki-67 Indicate?

What Does the Ki-67 Value in a Pathology Report Mean? What Does a High Ki-67 Indicate?
In this article

What Is Ki-67? How to Correctly Read the "Growth Rate" Number in Your Pathology Report

Many patients who see a line such as "Ki-67: 25%" in their pathology report wonder what the number means and whether a high value is bad news. Ki-67 is a measurement that shows what proportion of tumor cells are in the process of dividing at that moment; roughly speaking, it gives an idea of the tumor's "growth rate." On its own, however, it does not make a diagnosis, it does not determine the stage, and it does not tell a patient's future by itself. In this article, we explain how Ki-67 is measured, how it is used in breast cancer, neuroendocrine tumors and lymphomas, and the current recommendations of the International Ki-67 Working Group. We have previously covered, in separate articles, terms such as dysplasia, metaplasia and hyperplasia that often appear in pathology reports, HER2 positivity, biopsy and the history of the microscope in cancer pathology.

1983the year Ki‑67 was discovered in Kiel
5% · 30%reliable low and high cutoffs in breast cancer
3% · 20%grade boundaries in neuroendocrine tumors
G0resting cells contain no Ki‑67
Quick Answer · Physician Summary
  • What it measures: Ki-67 is a protein found in cells that are in the cell cycle and absent from resting cells. The percentage in the pathology report shows the proportion of tumor cells that stain.
  • High Ki-67: Shows that the tumor is multiplying faster. It generally points to a higher risk of recurrence, but also to a possibly better response to chemotherapy. On its own, it does not mean a "bad outcome."
  • Breast cancer: According to the international recommendation, only values of 5% or less and 30% or more can be interpreted reliably; values between 6% and 29% are a "grey zone." Decisions are not based on Ki-67 but on hormone receptors, HER2, tumor size, lymph node status and, when needed, genomic tests.
  • Neuroendocrine tumors: Ki-67 is the foundation of grading: below 3% is grade 1, 3–20% is grade 2, and above 20% is grade 3.

Why does this matter?

When cancer is diagnosed, the pathology report contains the most fundamental information about the tumor's type, grade and biological features. Ki-67 appears in almost every breast cancer report in particular, and it is one of the values patients ask about most. The problem is this: Ki-67 can be measured differently in different laboratories for the same tumor, its meaning changes with the type of cancer, and when it is misinterpreted it can lead to unnecessary worry or a wrong treatment decision.

Understanding Ki-67 correctly helps patients ask their doctors the right questions. For example, the same Ki-67 value may influence the chemotherapy decision in hormone receptor-positive breast cancer, while in triple-negative breast cancer it hardly changes treatment at all (breast cancer stages and treatment).

The first? The 40-year story of Ki-67
1983
Discovery in Kiel
Johannes Gerdes and his team found an antibody that recognizes only dividing cells. Its name comes from the city of Kiel, where the discovery was made, and from well number 67 on the experimental plate.
1990s
Entry into routine pathology
With the MIB-1 antibody, Ki-67 became measurable in paraffin blocks (routine pathology samples).
2011–2013
Subtypes in breast cancer
The St. Gallen consensus proposed dividing hormone-positive breast cancer into "luminal A" and "luminal B" based on Ki-67; the cutoff was debated first as 14% and later as 20%. The International Ki-67 Working Group published its first measurement recommendations.
2017–2019
Grading in neuroendocrine tumors
In the World Health Organization classification, Ki-67 became one of the main criteria that determine the grade of neuroendocrine tumors of the digestive system and pancreas.
2020–2021
Current breast cancer recommendations
The international working group stated that only values of 5% or less and 30% or more are reliable. The POETIC trial showed that the drop in Ki-67 after short hormone therapy before surgery predicts the risk of recurrence.
2021–2023
The first drug approval, and a reversal
In 2021, the FDA limited the use of abemaciclib after surgery to patients with Ki-67 of 20% or more; in March 2023, it removed this condition. The benefit had been seen regardless of Ki-67.
Today
Digital pathology and artificial intelligence
To reduce differences between laboratories, measuring Ki-67 with computerized image analysis and artificial intelligence is being studied.

What does the Ki-67 value in a pathology report mean?

The Ki-67 value shows what percentage of tumor cells are in the cell cycle at that moment. For example, if Ki-67 is 25%, about 25 of every 100 tumor cells counted have stained. The higher the value, the faster the tumor is thought to be multiplying. Ki-67 alone does not establish a diagnosis or stage; its meaning depends on the type of cancer, and it is interpreted together with the other pathology findings.

Figure 1 · How is Ki-67 measured?

Simplified diagram

Tumor tissue is examined with a special stainimmunohistochemistry · MIB-1 antibody Resting cell (G0)no Ki‑67nucleus does not stain Dividing cellG1 · S · G2 · M phasesKi‑67 present: brown Ki‑67 index (%)stained tumor cells ÷ tumor cells counted × 100
How to read it: The Ki-67 protein is present in all phases of the cell cycle (G1, S, G2, M); it is absent from resting cells that are not dividing (G0). Using a special stain, the pathologist sees the cell nuclei that contain Ki-67 as brown and calculates their proportion.

How is Ki-67 measured, and why do laboratories get different results?

Ki-67 is measured on a biopsy or surgical sample using a staining method called immunohistochemistry. The stained (brown) nuclei are counted and expressed as a proportion of all tumor cells. Although it looks simple, many factors affect the result:

  • Tissue preparation: For example, the time the sample spends in formalin, delays before fixation and the antibody used can change the result. The international recommendation advises that the sample be fixed in formalin for 6–72 hours and that a needle biopsy be used when possible.
  • Counting method: Some pathologists assess the most intensely stained area (the "hot spot"), while others assess the tumor as a whole. The international group recommends the "global" method, which represents the entire tumor.
  • Variation within the tumor: Ki-67 can differ between different areas of the same tumor; the result of a small needle biopsy can differ from that of the surgical sample.
  • Observer variation: Especially in the 10–20% range, different pathologists assessing the same slide can reach different results.

Figure 2 · What does Ki-67 of 25% mean?

Each square represents one tumor cell (example)

25 cells: Ki‑67 stained (in the cell cycle)75 cells: unstained (resting)
How to read it: If the nuclei of 25 of 100 tumor cells counted have stained for Ki-67, the Ki-67 index is 25%. In reality, the pathologist assesses hundreds, and if necessary thousands, of cells.

What Ki-67 means in different types of cancer

Cancer type Role of Ki-67 Effect on treatment decisions
Hormone-positive, HER2-negative breast cancer Helps estimate the risk of recurrence; used to distinguish luminal A from luminal B In early stages, considered in the chemotherapy decision together with other findings and genomic tests
Triple-negative and HER2-positive breast cancer Usually high; informative but not decisive Usually does not change the choice of treatment
Neuroendocrine tumors (digestive system, pancreas) The main criterion for grading Grade plays an important role in choosing treatment
Lymphomas Used in risk assessment for some subtypes (for example, mantle cell lymphoma) Varies by subtype
Brain tumors, sarcomas and others Supportive information Usually not decisive on its own

Same number, different meaning

Cutoffs used on the Ki‑67 scale (0–100); they vary by cancer type.

Hormone receptor-positive breast cancer (international recommendation)

grey zone
high (30% or more)

Neuroendocrine tumor (WHO grade)

grade 2
grade 3 (above 20%)
low: breast 5% or less · grade 1: below 3%breast: 6–29% grey zonegrade 2: 3–20%high / grade 3

Cutoffs are rounded. Lymphomas and other tumors use different cutoffs or have no fixed cutoff. WHO: World Health Organization.

Ki-67 in breast cancer

Ki-67 is discussed most often in breast cancer. In hormone receptor-positive, HER2-negative breast cancer, tumors with low Ki-67 are generally considered "luminal A," and those with high Ki-67 "luminal B"-like. Luminal A tumors grow more slowly and respond well to hormone therapy; in luminal B tumors, the risk of recurrence is higher and chemotherapy may be needed more often (treatment of hormone-positive breast cancer).

What do the international recommendations say?

  • Reliable ranges: Ki-67 of 5% or less can be considered low, and 30% or more high. At these two ends, agreement between laboratories is high.
  • Grey zone: For values between 6% and 29%, variation between laboratories is considerable; in this range, Ki-67 should not be used on its own to make treatment decisions.
  • Where it is used: The only supported use of Ki-67 is to provide prognostic information when deciding whether chemotherapy can be avoided in hormone receptor-positive, HER2-negative breast cancer with a tumor smaller than 5 cm and spread to 0–3 lymph nodes.
  • Genomic tests: For patients in the grey zone, genomic tests such as Oncotype DX and MammaPrint can provide more reliable information (genomic tests and clinical risk, patients who will not need chemotherapy, genomic tests in lobular breast cancer).

The drop in Ki-67 with hormone therapy before surgery

In the POETIC trial, in patients given an aromatase inhibitor for 2 weeks before surgery, a drop in Ki-67 below 10% was used as a sign of a good response to hormone therapy. Among patients whose Ki-67 was above 10% at baseline, the 5-year recurrence rate was 8.4% in those whose Ki-67 fell below 10% within 2 weeks, compared with 21.5% in those whose Ki-67 stayed high. This approach is used in some centers and studies, but it is not yet part of standard treatment.

POETIC: Ki‑67 drop and recurrence

5-year recurrence rate (%) by Ki‑67 status after 2 weeks of an aromatase inhibitor, in patients whose baseline Ki‑67 was above 10%.

Ki‑67 stayed above 10%
21.5%
Ki‑67 fell below 10%
8.4%

A rapid drop in Ki‑67 shows that the tumor is sensitive to hormone therapy. This approach is not yet part of standard treatment.

The abemaciclib example: why Ki-67 should not be the sole basis for a decision

In the monarchE trial, which showed the effect of abemaciclib in high-risk breast cancer after surgery, the FDA initially limited the approval in 2021 to patients with Ki-67 of 20% or more. However, later analyses showed that the benefit of abemaciclib was independent of the Ki-67 level, and in March 2023 the FDA removed the Ki-67 condition. This example shows that Ki-67 is not a measure that predicts treatment benefit, but one that helps estimate risk (monarchE 7-year results, CDK4/6 inhibitors).

Ki-67 in neuroendocrine tumors

In neuroendocrine tumors of the digestive system and pancreas, Ki-67 is one of the two main criteria that determine the tumor's grade in the World Health Organization classification; the other is the mitotic count, the number of dividing cells (mitoses) counted under the microscope. If the two point to different grades, the higher one is used.

Grade Ki-67 Mitotic count (per 2 mm²) General meaning
Neuroendocrine tumor, grade 1 Below 3% Below 2 Slow-growing
Neuroendocrine tumor, grade 2 3–20% 2–20 Moderately fast-growing
Neuroendocrine tumor, grade 3 Above 20% Above 20 Fast-growing, well differentiated
Neuroendocrine carcinoma (small cell or large cell) Usually very high (often above 55%) Above 20 Poorly differentiated, aggressive course

The distinction between a grade 3 neuroendocrine tumor and a neuroendocrine carcinoma is made not only on the basis of Ki-67 but on how the cells look under the microscope. Neuroendocrine carcinomas can also occur outside the digestive system (small cell neuroendocrine cancer of the cervix).

Lymphomas and other tumors

In lymphomas, Ki-67 helps in understanding the subtype and pace of the disease. For example, in Burkitt lymphoma Ki-67 is close to 100%, while in low-grade follicular lymphomas it is low. In mantle cell lymphoma, Ki-67 of 30% or more is associated with a less favorable course and is used in risk scoring (what is lymphoma, Hodgkin lymphoma). In brain tumors, sarcomas, prostate cancer and other cancers, Ki-67 provides supportive information but does not determine the treatment decision on its own (brain tumors).

What does high Ki-67 mean?

High Ki-67 shows that a significant portion of the tumor cells are multiplying, meaning that the tumor tends to grow faster. This generally means the following:

  • The risk of recurrence may be higher: Especially in hormone-positive breast cancer, high Ki-67 indicates a higher risk of recurrence if left untreated.
  • The response to chemotherapy may be better: Because chemotherapy acts on rapidly dividing cells, tumors with high Ki-67 generally respond better to chemotherapy. Complete response rates with chemotherapy before surgery are higher in these tumors (treatment before surgery).
  • It does not determine the outcome on its own: The tumor's type, size, lymph node status, hormone receptors, HER2 and the treatment given are far more decisive than Ki-67.
Common misconceptions
  • "If Ki-67 is high, the cancer has spread": No. Ki-67 shows the growth rate; spread (stage) is determined by imaging and pathology findings (what is metastasis).
  • "If Ki-67 is 80%, treatment won't work": No. Fast-growing tumors often respond better to treatment.
  • "It was 15% on the biopsy and 25% at surgery, so the disease has progressed": Usually not. Different samples and different areas can give different results; in addition, treatment given before surgery can lower Ki-67.
  • "If Ki-67 is low, no treatment is needed": No. Low Ki-67 is generally a good sign, but the treatment decision is based on all of the tumor's features.
The situation in Turkey

In Turkey, Ki-67 is routinely reported in pathology reports for breast cancer and neuroendocrine tumors; in many centers, it is also assessed in lymphomas and other tumors. However, the measurement method (hot spot or global scoring, by eye or by digital analysis) can differ from center to center. For this reason, especially for values in the 10–29% range, it is important not to compare results from different centers one-to-one and not to base treatment decisions on Ki-67 alone. Access to genomic tests and their cost vary by center and patient; when needed, this should be discussed with your doctor. Having the pathology slides re-examined at an experienced center is also an option (second opinion).

Questions to ask your doctor when you receive your pathology report

  • Which range is my Ki-67 value in? Is it low, in the grey zone or high, and what does that mean for my type of cancer?
  • Does it affect my treatment decision? For example, does it change whether I need chemotherapy?
  • Do I need a genomic test? Especially if my Ki-67 is in the grey zone in hormone-positive breast cancer.
  • What are the other findings? The tumor's grade, hormone receptors, HER2, tumor size and lymph node status.
  • Why are the biopsy and surgery results different? If there is a difference, ask about its cause and significance.

The pathology report is the foundation of the treatment plan; but rather than a single number, what matters is evaluating all the findings together. For basic concepts about cancer, see our guides on colon and rectal cancer, prostate cancer risk classification and pancreatic cancer, and for recent developments in breast cancer, our article what has changed since 2020.

Frequently asked questions

What does Ki-67 mean in a pathology report?
Ki-67 is a measurement that shows what percentage of tumor cells are in the cell cycle at that moment. For example, Ki-67 of 25% means that about 25 of every 100 tumor cells counted are multiplying. The higher the value, the faster the tumor is thought to be growing; however, its meaning depends on the type of cancer.
What Ki-67 level is considered high?
It depends on the type of cancer. In hormone-positive breast cancer, according to the international recommendation, 5% or less is considered low and 30% or more high; values in between are a grey zone. In neuroendocrine tumors, below 3% is grade 1, 3–20% is grade 2, and above 20% is grade 3.
Is high Ki-67 a bad sign?
High Ki-67 shows that the tumor is growing faster and that, if left untreated, the risk of recurrence may be higher. However, these tumors generally respond better to chemotherapy. Ki-67 does not determine the outcome on its own; the tumor's type, stage and other features are far more important.
Why is Ki-67 different on the biopsy and surgery reports?
Ki-67 can differ between different areas of the tumor, a needle biopsy shows only a small part of the tumor, and treatment given before surgery can lower Ki-67. The measurement method and tissue preparation also affect the result. Small differences usually do not mean that the disease has progressed.

Glossary

Ki-67
A protein found in the nucleus of cells in the cell cycle and absent from resting cells.
Immunohistochemistry
A pathology method in which specific proteins in tissue are stained with special antibodies so that they become visible under the microscope.
Proliferation
The multiplication of cells by division.
Luminal A / luminal B
Subtypes of hormone-positive breast cancer that grow more slowly (A) and faster (B).
Tumor grade
A measure of how closely tumor cells resemble normal cells and how fast they multiply.
Mitotic count
The number of cells seen dividing in a defined area under the microscope.
Genomic test
A test that estimates the risk of recurrence by measuring the activity of many genes in the tumor; for example, Oncotype DX and MammaPrint.
Prognosis
The expected course of the disease.

DROZDOGAN Academy Commentary

Ki-67 is one of the most frequently asked-about yet most easily misinterpreted values in pathology reports. It is an inexpensive, fast test that can be done almost anywhere; but it must be read in the right context.

⚡ Why it matters

In hormone-positive early-stage breast cancer, it contributes to the chemotherapy decision; in neuroendocrine tumors, it forms the basis of grading and therefore of treatment selection.

✅ Strengths

Wide availability, low cost, reliable prognostic information at the extremes (very low or very high values), and the ability to monitor response to treatment given before surgery.

⚠️ Limitations

Variation between laboratories and observers, low reliability especially in the 6–29% range, the lack of a standard counting method applied everywhere, and a limited role in predicting treatment benefit.

🩺 In practice

We do not interpret Ki-67 on its own but together with all of the tumor's biological and clinical features. In breast cancer, for patients in the grey zone, we use genomic tests when needed; in neuroendocrine tumors, we evaluate the Ki-67 result together with the mitotic count and the tumor's appearance.

❓ Open questions

Will digital pathology and artificial intelligence be able to eliminate differences between laboratories? Will the change in Ki-67 during treatment before surgery become a standard decision-making tool?

Bottom line: Ki-67 is a valuable measurement that reflects the tumor's growth rate, but it is not a verdict on its own. High Ki-67 may call for a more carefully planned treatment; low Ki-67 is generally a good sign. Correct interpretation is possible only by evaluating all the pathology findings together.

Transparency note
  • This article was prepared in October 2026.
  • The information is compiled from the current recommendations of the International Ki-67 in Breast Cancer Working Group, the World Health Organization classification of neuroendocrine tumors, the POETIC trial and FDA decisions.
  • The 25% value in Figure 2 is only an example. The cutoff values in the charts are rounded; different cancer types use different cutoffs.
  • This article is for general information only; it is not personal medical advice. Consult your doctor for the interpretation of your pathology report. The diagrams are derived from the text and contain no new data. The Academy commentary is our own.

References

  1. Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983;31:13-20. doi:10.1002/ijc.2910310104
  2. Nielsen TO, Leung SCY, Rimm DL et al. Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 2021;113:808-19. doi:10.1093/jnci/djaa201
  3. Dowsett M, Nielsen TO, A'Hern R et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 2011;103:1656-64. doi:10.1093/jnci/djr393
  4. Goldhirsch A et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus 2013. Ann Oncol 2013;24:2206-23. doi:10.1093/annonc/mdt303
  5. Smith I, Robertson J, Kilburn L et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC). Lancet Oncol 2020;21:1443-54. doi:10.1016/S1470-2045(20)30458-7
  6. FDA expands early breast cancer indication for abemaciclib plus endocrine therapy. ASCO Post, March 2023. ascopost.com
  7. Nagtegaal ID et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020;76:182-8. doi:10.1111/his.13975
  8. Hoster E et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma. J Clin Oncol 2016;34:1386-94. doi:10.1200/JCO.2015.63.8387
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