We herein administered combination-therapy using a personalized vaccination and the oral administration of UFT/UZEL for the treatment of either advanced or recurrent colorectal cancer. Safety and the efficacy of this new treatment modality were evaluated. Eight patients were enrolled in this clinical trial from July 2005 to May 2006. Up to 4 kinds of peptide vaccines which were selected according to the immune response of each patient were injected hypodermically every week. At the same time, UFT (300 mg/m2/day) and UZEL (75 mg/day) were also administered orally for 28 days followed by a 7-day rest period. Regarding the adverse events, callosity, a type of leukopenia, and liver-dysfunction, such as hyperbilirubinemia, an increase in the aminotransferase were observed. During the clinical evaluation after the end of the 2 courses, 3 cases showed progressive disease (PD) while 5 cases showed stable disease (SD). Our findings indicate that additional peptide vaccine therapy with UFT/UZEL, can be administered without compromising the patient's safety. Moreover, the use of UFT/UZEL does not normally interfere with the normal course of immune-therapy.