Medical oncologists are increasingly interested in identifying reliable prognostic factors for breast cancer in order to distinguish subsets of breast cancer patients and to optimize therapeutic approaches. Among them, the p53 tumor suppressor gene and bcl2 protein continue to be extensively studied, but their role remains to be defined. Moreover the mechanism of action by which they affect cell kinetics has to be clarified, particularly with respect to the balance between cell proliferation and apoptosis. We studied 138 operable breast cancer patients in order to verify the relationships of p53 and bcl2 proteins with better known clinicopathological features and their impact on the clinical outcomes of relapse-free survival (RFS) and overall survival (OS). Our data indicated a significant relationship between bcl2 expression and steroid receptor positive status, wild-type p53 and low proliferative index. Mutant p53 accumulation was found to be related to the absence of steroid receptors and high proliferation. Both were significant markers of better prognosis in univariate analysis. Multivariate analysis confirmed the favorable impact of bcl2 on both RFS and OS. On the contrary, we failed to observe any prognostic role for p53 status. We describe herein an independent favorable prognostic impact for patients with positive bcl2 expression that appears to be worthy of larger confirmatory study. On the contrary, our series seems to confirm the decreasing prognostic relevance of p53 in clinical practice.