Cholangiocarcinoma is a catastrophic tumor with a high mortality rate, for which surgery is the most reliable treatment. However, these tumors progress insidiously and are difficult to diagnose early. Most patients lack the opportunity to receive surgery due to the advanced disease stage at the time of the diagnosis, at which point only few alternative treatments are available. There is a need for more effective therapy to improve the survival or quality of life of these patients. The present case was a 73-year-old male who presented with jaundice and fatigue underwent CT imaging, in which a 3.5×4.0-cm low-attenuation mass was found in hepatic segment 4. Cholangiocarcinoma was diagnosed by cytological examination of the bile juice. A combination of CyberKnife radiosurgery and S-1 oral chemotherapy was performed. The patient was alive at a 8-month follow-up, and serial CT scans revealed a markedly regressed tumor. Therefore, we suggest that concurrent chemoradiation with the CyberKnife and S-1 is a treatment option for advanced cholangiocarcinoma. (Gut Liver 2010;4:103-105)