The purpose of this work was to determine if the immunohistochemical p53 (1) Bcl-2 (2) phenotype predicts survival in breast cancer patients. Tissue from 819 cases of resected primary breast cancer, presented between 1986 and 1998, were assembled in tissue microarray format. Clinicopathological data and prospective disease specific survival data were collected prospectively and immunohistochemical analyses of p53 and Bcl-2 expression were performed using antibodies DO-7 (p53) and 124 (Bcl-2) employing a standard IHC protocol. The expression data were correlated with clinicopathological variables and outcomes in both univariate (v 2 ) and multivariate (Cox's regression) analyses. Abnormal p53 expression and positive Bcl-2 expression were detected in 29% (193/673) and 46% (307/673) of tumours, respectively. On univariate analysis Bcl-2 expression was correlated with the clinicopathological features of less aggressive disease and loss of Bcl-2 expression correlated with a reduction in survival (log rank 5 11.91; p < 0.001). p53 expression correlated with the clinicopathological features of aggressive cancers and a reduction in survival (log rank 5 17.81; p < 0.001). Nineteen percent (127/673) of tumours displayed a p53 (1) Bcl-2 (2) phenotype. Kaplan-Meier analysis revealed a significant reduction in survival in these cases (log rank 34.01; p < 0.001). Multivariate analysis showed that while neither p53 expression nor Bcl-2 expression alone had independent prognostic significance, the p53 (1) Bcl-2 (2) phenotype remained independently associated with a worse prognosis (HR 1.79 95%CI 1.10-2.89 p 5 0.018).