The frequency of c-erb-B2 expression, clinical correlates and treatment outcome was investigated in 92 patients with metastatic breast cancer. Positive c-erb-B2 immunostaining was found in 24/92 (26%) of tumours. There was a statistically significant inverse correlation between c-erb-B2 expression and ER status. There was also a significant inverse correlation between c-erb-B2 expression and tumour free interval. c-erb-B2 expression had no influence on response to treatment with tamoxifen among patients co-expressing both c-erb-B2 and estrogen receptor (ER). Following chemotherapy (CAF) treatment there was a trend to a lower response rate among c-erb-B2+ as compared to c-erb-B2- patients. However, more c-erb-B2+ patients had received prior adjuvant chemotherapy, and when this factor was included in a multivariate analysis only prior adjuvant chemotherapy treatment predicted for response to CAF chemotherapy for metastatic disease. Time to treatment failure (TTF) was significantly shorter among cerb B2+ as compared to c-erb-B2- patients. The current study suggests that the c-erb-B2 expression is found at similar frequency in metastatic as in primary breast cancer. Although c-erb-B2 expression did not predict for response to either hormonal therapy or to chemotherapy for metastatic disease, patients with c-erb-B2+ metastatic lesions appear to have a more aggressive clinical course.