This study examined a combined treatment for colorectal carcinoma, the dual biochemical modulation therapy, consisting of 5-FU, Leucovorin (LV) and Cisplatin (CDDP). We compared its anti-tumor effects with other treatments: 5-FU alone, CDDP alone and 5-FU with LV. Primary diffuse infiltrated colorectal carcinoma is well known for its biological malignancy and its lack of response to chemotherapy. We used SRM cells from a cell line of carcinoma of the rectum, and subcutaneously injected them into nude mice. The anti-tumor effects were estimated from the growth rate, inhibition rate and thymidylate synthetase inhibition rates in the tumor tissue. Results indicated that even if the concentration of 5-FU and LV were reduced by half, these combined with CDDP were more effective than other therapies. Dual biochemical modulation therapy is particularly promising because the reduction of the dosages would reduce the side effects while still serving as an excellent anti-tumor therapy.