Delayed stool transit and other gastrointestinal abnormalities are commonly observed in persons with diabetes mellitus and are also known to be associated with colorectal cancer. Previous studies of the contribution of diabetes to colorectal cancer incidence and mortality have been limited by small sample sizes and failure to adjust for covariates. With more than 1 million respondents, the 1959-1972 Cancer Prevention Study provided a unique opportunity to explore whether persons with diabetes (n=15,487) were more likely to develop colorectal cancer during a 13-year follow-up period than were persons without diabetes (n=850,946). After adjustment for colorectal cancer risk factors, such as race, educational level, body mass index, smoking, alcohol use, dietary intake, aspirin use, physical activity, and family history of colorectal cancer, the incidence density ratio comparing colorectal cancer in those with diabetes and those without diabetes was 1.30 (95% confidence interval 1.03-1.65) for men and 1.16 (95% confidence interval 0.87-1.53) for women. However, diabetes was not associated with greater case fatality. Future studies should explore the possibility of a cancer-promoting gastrointestinal milieu, including delayed stool transit and elevated fecal bile acid concentrations, associated with hyperglycemia and diabetic neuropathy.