Distal cholangiocarcinoma (malignancy in the common bile duct from the cystic duct to the ampulla) remains a rare diagnosis. Most of these lesions are adenocarcinomas, and typically present with painless jaundice. If suspected, a high-quality CT scan and endoscopic retrograde cholangiopancreatography are required for diagnosis and staging. In addition, identification of risk factors, use of tumor markers, and advanced molecular testing may enhance diagnostic and prognostic capabilities. The treatment of choice for resectable disease is pancreaticoduodenectomy and the overall 5-year survival for resected distal cholangiocarcinoma remains 20% to 30%.