Cholangiocarcinoma at the choledochoduodenal anastomosis site is a rare complication. Our 71-years-old female patient developed an adenocarcinoma 38 years after cholecystectomy and choledochoduodenal anastomosis. During the previous two years she suffered from recurrent episodes of cholangitis and jaundice. Multiple endoscopically obtained biopsies from a suspicious area at the anastomosis showed a tubular adenoma. With a CA19-9 of 2,429 U/l laparotomy was performed with radical removal of the choledochoduodenostomy and the extrahepatic bile ducts and reconstruction with hepaticojejunostomy. The histological examination revealed a poorly differentiated, partly solid, partly tubular adenocarcinoma of the choledochal duct with metastasis of the lymph nodes in the hepatoduodenal ligament. According to the UICC staging system the tumor was pT2, G3, pN1 classified as stage III. Two months later the patient developed a peritoneal carcinosis with a CA19-9 of 15,050 U/l and died. The development of cholangiocarcinoma may be caused by chronic cholangitis, which may arise from several diseases of the bile ducts like choledochal cysts, primary sclerosing cholangitis or reflux of duodenal contents like in choledochoduodenal anastomoses. Because of the heterogeneity inside the lesions a malignant lesion can only be excluded by histopathological examination of the whole tumor.