<p>Although significant advances have been made in the molecular subtyping of breast cancers, identification of patients who do not benefit from the chemotherapy is a major challenge. Pioneer studies have examined the predictive value of the clinicopathological factors, such as tumor size, disease stage, the expression levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) molecules and more importantly tumor cells proliferation index (Ki-67) to help guide patients’ treatment and predict their outcome in the adjuvant chemotherapy setting. However, despite their clinical importance, no consensus is reached on their validity for chemotherapy decision. These challenges have ignited researchers to evaluate genomic signatures, which has led to the introduction of several genomic tests that can now help oncologists to include/exclude chemotherapy from the treatment regimen with more confidence. The present review aims to look back over the literature on the clinical significance of Ki-67 as well as the 21-gene recurrence score assay in identification of breast cancer patients who may benefit from the adjuvant chemotherapy.</p>