p63, a p53 homologue, is a myoepithelial cell marker in the normal mammary gland but p63-positive neoplastic cells may be found in up to 11% of invasive breast carcinomas. This study aims to verify the relationship between p63 expression and several clinicopathological features and tumor markers of clinical significance in breast pathology including key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors. Immunohistochemistry with 27 primary antibodies was performed in 100 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. p63-positive cells were found in 16% of carcinomas. p63-positive carcinomas were poorly differentiated, hormone receptor-negative neoplasms with a high proliferation rate. p63 also correlated with advanced pathological stage, tumor size, and the expression of human telomerase reverse transcriptase (hTERT), tissue inhibitor of matrix metalloproteinase 1 (TIMP1) and vascular endothelial growth factor (VEGF). The expression of TIMP1 suggests that the anti-proteolytic stimuli may be preponderant in p63-positive carcinomas. hTERT activity is associated with nodal metastases and cellular proliferation. VEGF regulates angiogenesis, which is also a fundamental event in the process of tumor growth and metastatic dissemination. Thus, the differential regulation of hTERT and VEGF in p63-positive breast carcinomas may contribute to the clinically more aggressive behavior of these neoplasms.