Klatskin-type cholangiocarcinoma is a rare tumor, bearing a very poor prognosis: at diagnosis, most patients can only undergo palliation. Evaluation of outcome, mean survival and quality of life was performed in patients with unresectable hilar cholangiocarcinoma treated with multimodality approach in comparison with surgical palliation, biliary stenting or brachytherapy alone. Twenty-six patients with hilar cholangiocarcinoma were studied: 16 patients were enrolled in the multimodality protocol (bilateral biliary drainage; Iridium-192 brachytherapy; plastic endoprosthesis or metallic stent positioning and external radiotherapy plus systemic chemotherapy), 5 patients underwent surgical palliation and 5 percutaneous decompression alone. Nine patients completed the protocol and 7 were treated with brachytherapy followed by biliary stenting alone. The multimodality approach obtained mean survival (10 months) similar to that for surgery and higher than that of the brachytherapy and metallic stenting groups (6 and 2.75 months, respectively). The average hospital stay (15 days) was lower than that of the surgical group (20 days). A multimodality approach is a suitable alternative to palliative surgery of unresectable hilar cholangiocarcinoma.