A 60-year-old Japanese man presented to our hospital for further investigation of an elevated serum anti-p53 antibody level. He was diagnosed with colon cancer and the tumour was surgically resected. Histological diagnosis of advanced colon cancer without lymph node involvement or distant metastasis was made. It was noteworthy that both serum carcinoembryonic antigen (CEA) and a fecal occult blood test that were performed preoperatively were non-diagnostic. This case highlights the potential usefulness of serum anti-p53 antibody tests for detection of colorectal cancers. Moreover, sequential changes in the anti-p53 antibody levels after curative resection were observed.