Sporadic colorectal cancer is a disease of the elderly. Some sporadic cancers are microsatellite unstable due to the silencing of the MLH1 mismatch repair gene through hypermethylation of its promoter region. The authors of this article found many of the 51 CpG sites to be methylated in the normal mucosa of patients with these cancers. The hypermethylation correlated strongly with advancing age. As shown, hypermethylation (blue signal) determined by a methylation specific in situ PCR method was evident in cytologically unremarkable cells that lined the surface of normal-appearing colonic glands. This hypermethylation is a candidate precursor lesion of cancer. (For details, see the article by Nakagawa et al. on p. 6991 in this issue.)