We studied the overexpression of c-erbB-2 protein in formalin-fixed, paraffin-embedded tissues from matched primary tumors and metastatic lymph nodes derived from each of 95 breast carcinoma patients. Twenty of 95 primary tumors (21%) exhibited positive membrane staining. Positive staining was also detected in the metastatic lymph nodes from 20 patients. In 19 patients overexpression of c-erbB-2 protein was observed in both primary and metastatic lymph nodes, indicating that there is a significant correlation between c-erbB-2 protein overexpression of primary and secondary metastatic lesion. Overexpression of the c-erbB-2 protein was observed at almost the same frequency regardless of clinical stage. The c-erbB-2 protein overexpression was associated with an absence of estrogen and progesterone receptors. Furthermore the overall survival and disease-free survival were reduced, although not significantly, in the patients with c-erbB-2 protein overexpression. Multivariate analysis indicated that overexpression of c-erbB-2 protein was a significant predictor of early relapse for node-positive patients. These results suggest that overexpression of the c-erbB-2 protein plays a role not only in an early stage but also in a metastatic stage in a certain patient subpopulation with breast carcinoma, and that c-erbB-2 protein overexpression analyzed by immunohistochemical techniques is of clinical significance in these patients.