The results of liver transplantation in patients with cholangiocarcinoma have been poor. It has been suggested that elevated serum CA19-9 levels predict cholangiocarcinoma in patients with primary sclerosing cholangitis. We analyzed the predictive value of CA19-9 antigen as a marker of cholangiocarcinoma in patients with primary sclerosing cholangitis evaluated for liver transplantation. We reviewed the charts of 26 patients with primary sclerosing cholangitis (stage IV) in whom preoperative serum CA19-9 levels were determined; 22 of 26 underwent liver transplant. Explant specimens were serially sectioned and examined for tumor. In 3 of the 26 patients, cholangiocarcinoma was diagnosed during pretransplantation evaluation; exploratory laparotomy on the last patient showed no evidence of cholangiocarcinoma, and this patient is awaiting transplantation. Twelve of the 26 patients had CA19-9 levels more than double the laboratory reference range (0-37 U/mL) (mean 183.1 +/- 103 U/mL, range 77-415 U/mL). Two of the 12 patients with elevated CA19-9 levels had cholangiocarcinoma. Of the 14 patients with normal levels, two had cholangiocarcinoma. No correlation between elevated CA19-9 and bile duct dysplasia was noted. Sensitivity for serum CA19-9 levels more than twice the reference range is 50%, specificity is 54.5%, positive predictive value is 16.6%. An elevated serum CA19-9 level in a patient with stage IV primary sclerosing cholangitis does not reliably predict coexisting cholangiocarcinoma. Persistently high or rising serum CA19-9 levels do not indicate more urgent need for liver transplantation.