In order to evaluate the involvement of cerbB-2 oncogene in the etiology and progression of breast cancer, DNA samples from 157 primary human mammary carcinomas were subjected to Southern and dot blot analyses for the presence of c-erbB-2 protooncogene alterations. None of 157 carcinomas analyzed showed c-erbB-2 rearrangement. Amplification of the c-erbB-2 was found in 28.6% (45/157) of the samples. Gene expression could be analyzed in only 97 of these tumors. High levels of c-erbB-2 transcripts were detected in 25.7% (25/97) of the tumor RNA preparations. Although there was a good correlation between c-erbB-2 overexpression and gene amplification, a significant proportion of the tumors showed overexpression in the absence of gene amplification or gene amplification without overexpression. A significant correlation between c-erbB-2 proto-oncogene alterations with the number of positive lymph nodes and tumor necrosis was found, suggesting that c-erbB-2 genetic alterations have a biological importance in the etiology of breast cancer.