The gene known as neu, erbB-2, or HER-2 is among those most frequently altered in human cancer, neu was first identified as a transforming gene activated in chemically induced rat neuroectodermal tumors [156, 202]. Subsequent work demonstrated that the neu proto-oncogene is a close relative of erbB, the gene encoding the EGFR (epidermal growth factor receptor), and neu was identified independently as a c-erbB-related gene, called c-erbB-2/HER-2 [15, 48,107, 192,255](Fig. 1). Early clinical studies linked changes in erbB-2 expression and gene copy number to several human cancers, notably breast, ovarian, and gastric adenocarcinomas. Owing to its accessible location at the cell surface, erbB-2 is now under intensive scrutiny as a therapeutic target. In this review we will summarize the involvement of the erbB-2 or neu gene in tumorigenesis. Since the role of erbB-2 in tumor development must be interpreted in the context of its normal functions, we will first describe the biology of the protein.