This study aimed to develop a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A breast cancer subtypes and assess the prognostic value of the Ki67 index in predicting recurrence-free and disease-specific survival. The study included 357 patients with invasive breast carcinomas, and gene expression profiling classified 101 (28%) as luminal A and 69 (19%) as luminal B. The optimal Ki67 cut point to distinguish luminal B from luminal A was 13.25%. In an independent cohort of 4046 patients, 2847 had hormone receptor-positive tumors, and using HER2 and Ki67 immunohistochemistry, 1530 were classified as luminal A, 846 as luminal B, and 222 as luminal-HER2 positive. Luminal B and luminal-HER2-positive tumors were associated with poor recurrence-free and disease-specific survival. For patients receiving tamoxifen as their sole adjuvant therapy, 10-year breast cancer-specific survival was 79% for luminal A, 64% for luminal B, and 57% for luminal-HER2 positive. The study concluded that ER, PR, HER2, and Ki67 expression can distinguish luminal A from luminal B breast cancers. The Ki67 index, a marker of cell proliferation, was found to be a clinically valuable biomarker for luminal B subtypes. The study highlights the importance of distinguishing luminal A and B subtypes for prognosis and treatment decisions. The results suggest that Ki67 and HER2 expression provide additional prognostic information beyond standard clinical parameters for hormone receptor-positive, lymph node-negative breast cancers. The study also found that luminal B and luminal-HER2-positive subtypes were associated with increased risk of recurrence and death compared to luminal A. The findings support the use of Ki67 and HER2 expression in clinical practice to guide treatment decisions for breast cancer patients.This study aimed to develop a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A breast cancer subtypes and assess the prognostic value of the Ki67 index in predicting recurrence-free and disease-specific survival. The study included 357 patients with invasive breast carcinomas, and gene expression profiling classified 101 (28%) as luminal A and 69 (19%) as luminal B. The optimal Ki67 cut point to distinguish luminal B from luminal A was 13.25%. In an independent cohort of 4046 patients, 2847 had hormone receptor-positive tumors, and using HER2 and Ki67 immunohistochemistry, 1530 were classified as luminal A, 846 as luminal B, and 222 as luminal-HER2 positive. Luminal B and luminal-HER2-positive tumors were associated with poor recurrence-free and disease-specific survival. For patients receiving tamoxifen as their sole adjuvant therapy, 10-year breast cancer-specific survival was 79% for luminal A, 64% for luminal B, and 57% for luminal-HER2 positive. The study concluded that ER, PR, HER2, and Ki67 expression can distinguish luminal A from luminal B breast cancers. The Ki67 index, a marker of cell proliferation, was found to be a clinically valuable biomarker for luminal B subtypes. The study highlights the importance of distinguishing luminal A and B subtypes for prognosis and treatment decisions. The results suggest that Ki67 and HER2 expression provide additional prognostic information beyond standard clinical parameters for hormone receptor-positive, lymph node-negative breast cancers. The study also found that luminal B and luminal-HER2-positive subtypes were associated with increased risk of recurrence and death compared to luminal A. The findings support the use of Ki67 and HER2 expression in clinical practice to guide treatment decisions for breast cancer patients.