Aberrant methylation of the CHFR gene associated with gene silencing has been reported in several primary tumors. In order to define the role of CHFR in the tumorigenic pathway of the colorectum, the methylation of CHFR was examined in tumors from colorectal cancer patients. Ninety-eight colorectal cancer patients were examined using a methylation-specific PCR (MSP) for CHFR CpG island in primary tumors. An aberrant methylation of the CHFR gene was detected in 25 out of 98 (26%) primary colorectal cancers. No methylation was detected in the corresponding normal tissue specimens. This finding suggested that an aberrant methylation of the CHFR gene occurs frequently in colorectal cancers. After a methylation analysis of all samples, the clinicopathological data were correlated with these results. A significant difference was found in the tumor (p=0.035), thus, indicating that in early colorectal cancer the CHFR gene was more frequently methylated than in advanced cases. These findings suggest that CHFR might act as a tumor suppressor in at least some colorectal cancers and that CHFR methylation might, therefore, be a particular phenomenon of early colorectal cancer.