The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. The association of HER-2/neu gene and protein abnormalities with prognosis in breast cancer is presented by considering a series of 52 published studies including more than 16,000 patients. The relative advantages and disadvantages of Southern blot testing, polymerase chain reaction amplification, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed with immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The importance of HER-2/neu protein overexpression in ductal carcinoma in situ, and HER-2/neu protein status in uncommon breast diseases in female patients and breast cancer in male patients are also considered. The potential value of HER-2/neu protein status for the prediction of response to therapy in breast cancer is presented for standard hormonal therapy, cytotoxic chemotherapy, and radiation therapy. Also evaluated is the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response. Finally, preliminary data concerning use of antibody-based therapies directed against HER-2/neu protein and their potential use in breast cancer treatment are considered.