Carcinomas of the extrahepatic bile ducts are uncommon neoplasms that are morphologically heterogeneous and associated with a poor prognosis. We have previously shown that the noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts behave as in situ carcinomas and are associated with a better prognosis. We reviewed the clinical records of 13 patients with invasive papillary carcinomas of the extrahepatic bile ducts and analyzed the microscopic features and selected immunohistochemical reactivity (p53, Mib-1, and Dpc4) that might correlate with patient survival. In addition, we present the updated SEER (Surveillance, Epidemiology, and End Results) data of the National Cancer Institute for the invasive extrahepatic bile duct carcinomas compiled from 1975 to 1998. The 13 patients with papillary carcinoma had a male to female ratio of 1:1, and their ages ranged from 33 to 89 years. Painless jaundice and abdominal pain were the most common complaints. Five tumors were located in the distal portion, one in the mid portion, and six in the proximal portion of the common bile duct. One papillary carcinoma arose in the right hepatic duct. The Whipple procedure was performed in six patients, common bile duct resection in six, and right hepatic lobectomy in one. The cell phenotype of the papillary carcinomas was biliary in nine and intestinal in three. One tumor had both biliary and intestinal phenotypes. Four tumors dedifferentiated (two to undifferentiated small cell carcinomas, one to small [oat] cell carcinoma, and one to giant cell carcinoma). Two papillary carcinomas extended into the pancreas and three into the liver. Only one patient had lymph node metastases at presentation. Follow-up was available in 10 patients. Six patients died of disease from 2 weeks to 2 years and 1 month after surgery. Four patients are alive with no evidence of disease from 4 months to 8 years and 8 months after surgery. Of 174 invasive papillary carcinomas compiled by the SEER program, 71 were confined to the ductal wall, and 61 had regional lymph node metastases. Papillary carcinomas confined to the ductal wall have better 10-year relative survival rates than adenocarcinomas limited to the wall (21% versus 12%). Likewise papillary carcinomas with lymph node metastasis have better prognosis than adenocarcinoma with nodal metastases (10-y survival rate of 12% versus 5%). Currently, the histologic type and the stage of the disease are the most important prognostic factors in these papillary carcinomas. Separation of invasive and noninvasive or minimally invasive papillary carcinoma is critical in estimating the patient outcome. Our findings suggest that there is no correlation between p53, Ki-67, and Dpc4 expression in these tumors and survival of the patients.