We investigated the usefulness of serum anti-p53 antibody (anti-p53) measurement for the diagnosis of colon cancer. carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and anti-p53 were measured by enzyme-linked immunosorbent assay in 375 colorectal cancer patients and 115 healthy volunteers(control group). When the cut-off level of the serum anti-p53 antibody was set to 1.3 U/mL, 114 (30.4%) of the colorectal cancer patients tested positive. Twelve positive cases(10.4%) were recognized in the control group. The median levels of anti-p53 were 0.69 U/mL(0.69- 10,610) and 0.69 U/mL (0.69-19.5) in the colorectal cancer patients and control group, respectively. The positive rates of CEA level (cut-off value 6.7 ng/mL) and CA19-9 level (cut-off value 37 U/mL) were 40.0% and 18.9%, respectively. Of these tumor markers, positive cases with only anti-p53 were observed in 60 patients (16%). The positive rate of all markers examined was 61.6%. No significant correlation was observed between the level of anti-p53 and other markers. The positive rates of anti-p53 in each stage of the colon cancer patients were as follows: stage 0 and I, 19.4%; stage II, 27.0%; stage III,36.1%; and stage IV,61.0%. The positive rate of anti-p53 was higher than that of CEA and CA19-9 in the early stages of colorectal cancer. Furthermore, a combination of these markers improved the diagnosis of colorectal cancer by approximately 60%. These results suggest that the measurement of anti-p53 is useful for diagnosis of colorectal cancer in clinical practice.