A provocative array of observations from both laboratory and clinical investigations indicates that alterations in folate status modulate the process of neoplastic transformation in selected epithelial tissues. Diminished folate status appears to promote carcinogenesis. Considerably more speculative is the concept that supraphysiologic folate status may afford some protection against cancer. Although observations to this effect support such a relationship in the uterine cervix, lung, stomach, and esophagus, present evidence clearly is most compelling for the colorectum. This article reviews these observations, particularly as they apply to the colorectum, and outlines some of the possible mechanisms by which these effects may be exerted.