The c-erbB-2 protein was measured in sera of patients with breast cancer or benign breast diseases to study the significance of this protein as a tumor marker. The mean value and positive rate for this protein (assuming 20U/ml as the cut-off value) were 11.8 U/ml (0%) in benign breast disease (n = 30), 11.8 U/ml (3.1%) in stage I/II primary breast cancer (n = 64), 38.2 U/ml (29.4%) in stage III/IV primary breast cancer (n = 17), 17.9 U/ml (33.3%) in locally recurrent breast cancer (n = 12), 298.4 U/ml (51.0%) in recurrent breast cancer with distant metastases (n = 51), and 12.9 U/ml (0%) in those with no evidence of recurrence (n = 57). Thus, the serum c-erbB-2 protein level was significantly higher in the distant metastatic group. In patients with distant metastases, there was a close association between expression of c-erbB-2 protein in the primary tumor and the serum c-erbB-2 protein level. On the basis of these results, serum c-erbB-2 protein was thought to be useful as a tumor marker for postoperative monitoring of breast cancer, especially in patients positive for expression of this protein in primary cancer tissue.