Tumor tissue from patients with advanced breast cancer was analyzed for HER-2/neu and p53 expression. The tissue samples from primary tumor and from axillary lymph nodes or distant metastases from 118 breast cancer patients were obtained. Sections from formalin-fixed, paraffin-embedded materials were immunostained for HER-2/neu and p53 oncoprotein expression. Staining results were correlated with survival times and disease-free survival times, flow cytometric synthesis phase fractions, and DNA ploidy. No correlation could be found between HER-2/neu and p53 or any other tested factor, but grade I primary cancers that were positive for HER-2/neu showed a tendency for better outcome. The HER-2/neu staining of the metastases was independent of the staining of the primary tumor. HER-2/neu can be used as a prognostic marker for advanced breast cancer, when the primary tumor is well differentiated.