Overexpression of the c-erbB-2 proto-oncogene has been shown to correlate with relapse and poor prognosis in adenocarcinomas of the breast and stomach. In pancreatic cancer, c-erbB-2 overexpression has been demonstrated using immunohistochemistry, but the relationship between serum c-erbB-2 level and clinical data has not been fully evaluated. In this study, serum c-erbB-2 protein levels were measured in 100 patients with pancreatic adenocarcinomas and in 9 patients with mucin-producing tumors. Immunohistochemical studies for c-erbB-2 protein were performed in 36 patients and 4.0 U/ml in healthy controls (p < 0.001). The positive rate for serum c-erbB-2 was 34% (37/109) in patients with pancreatic cancer and 0% (0/66) in patients with gallstones and in healthy controls (p < 0.001). Immunohistochemical study disclosed that the positive staining rate was 28% (8/29) in common ductal adenocarcinoma specimens, 43% (3/7) in metastasis specimens, and 75% (3/4) in mucin-producing tumor specimens. Clinical evaluation revealed that 59% (22/37) of serum c-erbB-2-positive patients and 33% (24/72) of negative patients had liver or peritoneal metastases (p < 0.01). The mean survival time was 154 days in the c-erbB-2-positive group and 220 days in the negative group (p < 0.05). We suppose that c-erbB-2 is related to metastasis and progression of the disease in patients with advanced pancreatic cancer.