Using cloned v-erbB as a probe, we have detected abnormalities of two closely related proto-oncogenes in human tumor samples. Abnormalities of the c-erbB 1 gene, the epidermal growth factor receptor, have been identified as gene amplification without apparent abnormalities of the mRNA. Gene amplification in a human mammary carcinoma allowed us to identify and characterize a second and distinct member of this proto-oncogene family, c-erbB 2. The latter is currently under intensive study at the level of the gene mRNA and protein to determine its functional role in both normal and malignant cells. Recently we have used a similar approach to isolate and partially characterize a second member of the abl proto-oncogene family, termed arg, an abl-related gene.