Overexpression of the c-erbB-2/HER2 protooncogene in breast carcinoma is controlled not only by the degree of amplification of the gene but also at the level of gene transcription. Thus, whether or not the gene is amplified, the activity of the c-erbB-2 promoter is enhanced in overexpressing cells through the binding of an additional transcription factor, OB2-1, whose activity is increased in these lines. Here we describe further characterization of OB2-1 and show that it is identical to the developmentally regulated transcription factor AP-2. Functional assays confirm that AP-2 is able to regulate c-erbB-2 expression in mammary-derived cell lines. Furthermore, although AP-2 is barely detectable in cells with the low c-erbB-2 expression phenotype, protein levels are clearly elevated in a panel of c-erbB-2-overexpressing lines. These findings demonstrate an important role for this transcription factor in human cancer.