We performed preoperative chemoradiotherapy in locally advanced cases of rectal cancer without distant metastasis. The methods for drug administration and irradiation were as follows: oral administration of S-1 at 80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33, with periods of 5 days on drug and 2 days off drug and intravascular administration of CPT-11 for 120 minutes on days 1, 8, 22, and 29, at doses of 60 mg/m2/day in Case 1 and 70 mg/m2/day in Case 2. The radiation dosage was a fractionated exposure of 1.8 Gy/day x 5 days/week for 5 weeks, for a total of 45 Gy. No major adverse events were observed in either case, and the treatment was performed as per the protocol. No postoperative complications were observed in either case. Both patients showed complete pathological remission with no evidence of tumor cells in the primary focus and no lymph node metastases. Preoperative chemoradiotherapy with a combination of S-1 and CPT-11 may be a new treatment for rectal cancer.