More than a quarter of a century has elapsed since the identification of the c-src proto-oncogene. During that period, we have learned that cancer arises as the result of mutations in proto-oncogenes and tumor suppressor genes, and we are now seeing the first fruits of these discoveries, in the form of targeted therapies directed against activated tyrosine kinases such as Bcr-Abl, c-Kit and the EGF receptor. But the discovery of the c-src proto-oncogene was in turn based on decades of study on an avian RNA tumor virus, Rous sarcoma virus (RSV). Here I review the work that led up to the identification of the RSV transforming gene and its protein product, and how this information in turn led to the discovery of cellular Src.