Warfarin is one of the most commonly used oral anticoagulant. It is well established that a wide range of drugs, including the anticancer drug 5-fluorouracil, interact with warfarin; this results in altered coagulation parameters and bleeding sequelae. To date, any drug interaction between warfarin and TS-1 has not been reported on. A 58-yr old woman visited emergency department with gross hematuria and soft tissue swelling involving her left thigh and buttock. She had been diagnosed as having advanced colon cancer (Duke's classification D); she had undergone right hemicolectomy and partial hepatectomy, and she had received 5-FU/leucovorin chemotherapy two years prior to admission. Recurrent disease was revealed in the liver and lungs, and so 6 cycles of FOLFIRI (5-FU, leucovorin and irinotecan) chemotherapy were given. Follow-up abdominal CT scan showed progressive disease and then TS-1 oral chemotherapy was started. She took warfarin 2mg per day because of partial thrombosis in the lower inferior vena cava and left ovarian vein. The initial laboratory tests revealed a prothrombin time of 120 seconds and an international normalized ratio of 35. Fresh frozen plasma and a parenteral vitamin K injection were given. After resorption of the subcutaneous hematoma, warfarin was restarted at a dose of 1mg per day. This case shows the significant increased bleeding tendency following the combined administration of warfarin and TS-1. Because of the potential severity of this interaction, close monitoring of the coagulation parameters is recommended for patients receiving warfarin together with TS-1.