Since January 1985, 12 patients with local/regional extrahepatic biliary system cancer (2: gallbladder; 5: Klatskin; and 5: common bile duct) underwent combined modality therapy. An endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiogram, and biliary drainage were performed in 5 patients, and 7 patients underwent laparotomy and biopsy or subtotal resection. All patients initially received 5,000 cGy to the tumor bed and primary nodal area and 10 received an additional 1,500-cGy boost to the tumor bed. Chemotherapy (5-fluorouracil/mitomycin-C) was delivered at the beginning of each radiation treatment course. Four patients received an additional 1-4 cycles of maintenance chemotherapy and 7 received a boost with brachytherapy. The median survival was 17 months and the overall 4-year actuarial survival was 36%. Four patients have no evidence of disease at 16, 30, 48, and 64 months, respectively. The patterns of failure as a component of failure were local/regional progression, 50%; abdominal failure, 58%; and distant failure, 8%. Of the 8 patients who developed failure, 6 developed a component of local/regional progression. Our data continue to show that this approach is feasible and may result in an improvement in survival. Continued follow-up will be needed to determine the ultimate impact of this aggressive approach.