Assays based on the molecular detection of genetic changes in serum have been shown as potential diagnostic tools for colorectal cancer. We examined the methylation status of p16 in colorectal cancers using methylation-specific PCR (MSP). Forty-four of 94 (47%) cancer DNA exhibited abnormal promoter methylation of p16 gene while no corresponding normal DNA exhibited such methylation. Subsequently, we examined whether aberrant methylation could be detected in corresponding serum DNA, and found that 13 of 44 (30%) patients with p16 promoter methylation in tumor DNA demonstrated abnormal methylation in their serum DNA. Moreover, abnormal methylation was found in the serum of patients in all clinical stages, suggesting that early colorectal cancer could be detected using the MSP method.