Previous reports showed that breast and gastric cancers overexpressing c-erbB-2 protein have a greater metastatic potential and worse prognosis than tumors in which this protein is not overexpressed. The present study was undertaken to examine the significance of c-erbB-2 protein expression as a prognostic factor in colorectal cancer. Protein expression was examined immunohistologically in colorectal cancer tissue from 149 patients without distant metastasis, from 38 patients with liver metastasis, and from 18 patients with lung metastasis. The c-erbB-2 protein-positive rate was significantly higher in cases with lymphatic vessel invasion in the primary tumor, but it did not correlate with lymph node metastases. Expression of c-erbB-2 did not correlate with any other histologic feature (histologic type, depth of tumor invasion, venous vessel invasion, or the clinical stage). The positive rate in the primary lesion was significantly higher in cases with liver metastasis than in cases without liver metastasis, the positive rate was significantly higher in the hepatic than in the primary lesions. The expression of c-erbB-2 protein in colorectal cancer tissue correlates closely with liver metastasis but not with lymphatic or lung metastases.