Increased Ki-67 expression is associated with worse prognosis in patients with triple-negative breast carcinoma (TNBC); Ki-67 is widely used as a prognostic marker for TNBC patients. p16 and p53 are tumor suppressors. The status of p53 expression can divide TNBCs into 2 biologically distinct subgroups. The relationship of p16 expression with Ki-67 and its association with the status of p53 in TNBC patients have not been well characterized. In this study, we investigated p16 expression in 60 high-grade invasive TNBC cases and its relationship with Ki-67 in different groups of TNBCs and correlated p16 with Ki-67 in p53-positive and p53-negative subgroups. The tumors were immunolabeled for p16, Ki-67, and p53. Tissue microarrays were constructed with each tumor and adjacent normal breast tissue. Of the 60 tumors, 45 (75%) were found to have p16 expression. The triple-negative tumors had significantly higher p16 expression compared with paired normal ducts (P < .0001). Mean expression level of Ki-67 in p16-positive tumors was significantly higher than that in p16-negative tumors regardless of the status of p53 (P < .05). p16 expression positively correlated with Ki-67 (69.05% ± 7.23%) in the 22 p53-negative tumors (r = 0.739; P < .001). However, no correlation was found between p16 and Ki-67 (77.2% ± 3.83%) in the 38 p53-positive tumors (r = 0.157; P = .424). These findings suggest that p16 may play a role in the proliferation and aggressiveness of p53-negative TNBC and provide insights into the potential prognostic value of p16 as well as a better understanding of tumor biology related to the Rb/p16 pathway abnormalities.