Cholangiocarcinoma involving the distal common bile duct (distal cholangiocarcinoma [DCC]) is a periampullary neoplasm that is less common than, but often difficult to distinguish from, pancreatic adenocarcinoma (PDA). The prognosis and cure rate of DCC is improved over that of PDA, but it remains a highly lethal disease. Although the diagnostic and therapeutic management of DCC is not dissimilar from PDA, the pathophysiology is, in many instances, distinctly different. A multi-disciplinary approach toward DCC is important.