Malignant tumors may arise from any portion of the biliary tree. The term cholangiocarcinoma (CC) applies to both intra- and extrahepatic tumors. More than 95% of these tumors are adenocarcinomas. Differentiation between CC and metastatic adenocarcinoma represents a difficult task for the pathologist. The presence of an intratumoral mini-ductal plate, and in situ carcinoma in bile ducts near the tumor and modulation from the bile duct towards parenchymal liver cells represent the major criteria in assessing the identity of an adenocarcinoma as a primary CC. Primary sclerosing cholangitis and congenital bile duct cysts both put patients at risk of developing CC. Lithiasis, recurrent pyogenic cholangitis, and typhoid infection are suspected but not proven predisposing conditions. Fluke infestations (Clonorchis sinensis and Opisthorchis viverrini) play a role in Far Eastern countries. Bile duct adenoma and multiple biliary papillomatosis may carry a malignant transformation potential. Pseudopyloric metaplasia may be a precursor lesion of CC.