HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.