Using a specific antiserum (21N) to the c-erbB-2 oncoprotein, a total of 405 primary malignant human tumors arising in the breast (n = 191), lung (n = 110), colon/rectum (n = 23), bladder (n = 48), prostate (n = 23), and skin (n = 10) were stained immunohistochemically to detect those tumors that over-expressed this putative transmembrane receptor. Malignant cells showed intense positivity for this oncoprotein in 17% of the breast carcinomas, 4% of the colorectal tumors, 2% of the bladder tumors, and 1% of the nonsmall cell lung carcinomas. No positive staining was evident in the prostate, skin, or small cell lung carcinomas. This study shows that over-expression of the c-erbB-2 oncoprotein is common in breast cancer but relatively rare in the other malignancies studied. In addition, this oncoprotein can be identified readily in routine paraffin-embedded tissue.