An increased risk of colon cancer has been observed in individuals with long-standing ulcerative colitis (UC). In order to identify molecular genetic markers for the development of neoplasia in UC individuals, we isolated DNA from normal, regenerative, and dysplastic mucosa, as well as from colon carcinomas from UC patients, and evaluated it for the presence of mutations in microsatellite DNA sequences. DNAs isolated from regenerative mucosa displayed microsatellite mutation. These observations suggest that DNA mutation is an early event in the UC disease process.