HER-2/neu (also known as c-erbB-2) oncogene is a member of the epidermal growth factor receptor family and its amplification is one of the most common genetic alterations associated with human breast cancer. Preclinical studies have suggested that HER-2/neu overexpression enhances metastatic potential of breast cancer cells. Although some discrepancies exist in clinical studies, in general, HER-2/neu amplification is found to be associated with more aggressive clinicopathologic features. HER-2/neu amplification is also associated with drug resistance or sensitivity to specific chemotherapy and hormonal therapy regimens. Advances in breast cancer therapies in recent years have moved towards the development of tumor-specific targeted therapies. Monoclonal antibodies directed against HER-2/neu have been developed and used in clinical practice. These developments necessitate a reliable assay for assessment of HER-2/neu. This article is a review of biologic and clinical significance of HER-2/neu and summarizes HER-2/neu detection methods.