Breast cancer is one of the most significant health concerns worldwide. The discovery of molecular changes at the gene level represents a critical milestone toward the development of novel targeted therapy specific to cancer cells. The recognition of the significance of the HER-2/neu oncogene is a landmark in the treatment and prognostication of breast cancer. The human epidermal growth factor 2, HER-2/neu (c-erbB- 2) oncogene, a member of the growth factor receptor family, is amplified in 10-34% of patients with invasive breast cancer and associated with more aggressive disease and poorer prognosis. The development of an immunotherapeutic, trastuzamab (Herceptin), to the extracellular domain of HER-2/neu has provided significant improvements in the outcome of HER2 positive breast cancer patients in the adjuvant, neoadjuvant and metastatic setting. This paradigm shift in breast cancer treatment has made it imperative to measure HER-2/neu amplification status to correctly identify and assign breast cancer patients for Herceptin therapy. There is an increasing demand for the development of clinically meaningful and reproducible assays for HER-2/neu on archived and prospective histological and cytological samples, their integration with prospective molecular methods and therapeutics is a challenge that pathologists must now address. This review focuses on current and future methodologies for measuring HER-2/ neu in breast cancer and also includes a synopsis on the role of HER2/neu gene in breast cancer, its association with histological types and grades, familial and male breast cancer.