The levels of c-erbB-2 oncoprotein (ErbB-2 protein) in nipple discharge were evaluated together with those of carcinoembryonic antigen (CEA) in 9 patients with breast cancer, 2 patients with borderline lesions, 8 patients with intraductal papilloma, and 19 patients with fibrocystic change. When the tentative cutoff value was set at 40 ng/ml in the nipple discharge, elevated ErbB-2 protein levels were found in all 3 patients with palpable breast cancer and 3 of the 6 patients with nonpalpable cancer. Two of the 8 patients with intraductal papilloma had high ErbB-2 protein levels. A combination test with CEA resulted in positive detection in all cancer patients. Two patients with borderline lesions, 2 with intraductal papilloma and 2 with ñbrocystic change were positive in a combination test. In addition, elevated ErbB-2 protein levels in nipple discharge correlated well with the overexpres-sion of ErbB-2 protein in the tumor. All the patients with ErbB-2 protein levels over 100 ng/ml in their nipple discharge had comedo or solid intraductal carcinomas. Thus, measurement of ErbB-2 protein levels in nipple discharge can assist in the diagnosis of intraductal carcinoma and also in detecting tumors with a high proliferation rate and an overexpression of ErbB-2 protein: usually comedo or solid carcinomas