The purpose of this study was to evaluate how the outcome of patients with extrahepatic cholangiocarcinoma (EHBC) may have been influenced by tumor location and treatment selection. The primary endpoint of this study is overall survival (OS). Between January 1983 and December 1997, 221 patients with biliary tumors were evaluated at Thomas Jefferson University Hospital. Of these, 118 fit the inclusion criteria for this study. The extent of disease was assessed by computed tomography, percutaneous transhepatic cholangiography or endoscopic retrograde cholangiopancreatography, magnetic resonance imaging, and ultrasonography. All patients had histologic confirmation of malignancy. Roux-en Y, hepaticojejunostomy, or choledochojejunostomy followed surgical resection of the primary tumor. Palliative measure (PS) included biliary catheter placement without brachytherapy or external beam irradiation (RT). RT was delivered via high-energy photons. Intraluminal brachytherapy was performed via percutaneous biliary catheterization with iridium-192 ribbon sources. Chemotherapy consisted of either intravenous 5-fluorouracil alone or in combination with doxorubicin, mitomycin C, or paclitaxel. PS consisted of metal bile duct stent placement. Median follow-up time for the entire group was 102 months and 43 months for patients who were still alive at the conclusion of the study period. Patients with proximal tumors underwent resection (n = 5), surgery and RT (n = 23), RT only (n = 31), chemotherapy only (n = 6), or PS (n = 12). Patients with distal tumors were treated with surgical resection (n = 17) or a combination of surgery and RT (n = 13), RT only (n = 6), or PS (n = 4). Median survival time (MST) for all 118 patients was 22 months. The MST for patients with distal tumors was 47 months versus 17 months for those with proximal tumors. The MST has not been reached for patients with distal EHBC treated with surgical resection and postoperative RT, whereas the median survival for those treated with surgery alone is 62.5 months. However, 4 of 17 of these patients had in situ carcinoma. Six patients had distal tumors treated with RT only with a MST of 6 months. Patients with proximal tumors treated with surgery and RT had a superior OS at 5 years compared to patients treated with RT alone (24 vs. 13 months; p = 0.007). There was an improved OS in patients with proximal tumors treated with surgical resection and RT compared to surgery alone (p = 0.023). There is no discernable influence of chemotherapy on outcome in patients with proximal EHBC. The MST for patients treated with PS was 3.5 months. Surgery and postoperative RT appear to be better than either surgery or RT alone in patients with proximal EHBC. In patients with distal EHBC, the addition of resection and RT appears to offer an advantage, which is increasingly apparent with longer follow-up time. The prognosis remains dismal for patients treated with palliative intent.