BACKGROUND Selenium is an essential trace element found in cereals, wheat, dairy products, meat, and fish. This micronutrient may prevent carcinogenesis through several biochemical pathways; one suggested pathway is enhanced apoptosis. OBJECTIVES The relation between selenium and colorectal adenomas was evaluated because the colorectal adenoma is the established precursor lesion of most colorectal cancers. Apoptosis was a pathway of interest because decreased apoptosis has been associated with an increased prevalence of adenomas. Our objectives were as follows: to investigate the association between (a) selenium and colorectal adenomas and (b) selenium and apoptosis. METHODS The study population was assembled for the Diet and Health Study III (n = 803), a cross-sectional study conducted at the University of North Carolina Hospital (Chapel Hill, NC). There were 451 participants in the analysis of selenium and adenoma prevalence and 351 participants in the analysis of selenium and apoptosis. Selenium was measured from serum collected at the time of colonoscopy. Apoptosis was measured in biopsies from normal rectal epithelium obtained during the colonoscopy procedure. RESULTS Participants in the highest fifth of serum selenium were less likely to have adenomas in comparison with those in the lowest fifth (prevalence ratio, 0.6; 95% confidence interval, 0.4-1.1). Selenium and apoptosis (>2.76 cells per crypt) were not strongly related, but results collectively suggested a roughly inverse association. CONCLUSIONS High selenium was associated with a reduced prevalence of colorectal adenomas. Apoptosis, however, did not seem to be the mechanism by which selenium was related to adenoma prevalence in our data.