The biology of breast carcinoma is complex, with multiple factors contributing to its development and progression. The current review focuses on the role of several critical genes including estrogen receptor, progesterone receptor, retinoic acid receptor-β, epidermal growth factor receptor family members, p53, BRCA1, and BRCA2 as risk factors for the development of disease, predictors of prognosis and response to therapy, and as therapeutic targets. Studies of the biology of these and other genes that contribute to the development and progression of breast carcinoma have had and will continue to have great impact on all aspects of disease management. Cancer 2003;97(3 Suppl):825–33. © 2003 American Cancer Society.