The relationship between diet diversity (i.e., variety in food intake computed as the total number of foods consumed at least once per week) and the risk of colorectal cancer was investigated using data from a hospital-based, case-control study carried out between 1985 and 1992 in Northern Italy. Subjects were patients with histologically confirmed incident cancers of the colon (n = 828) and rectum (n = 498) and 2024 controls admitted for acute, nonneoplastic, non-digestive tract conditions. A significant inverse association (multivariate relative risk, 0.7) for the highest (more diverse diet) versus the lowest quartile of total diet diversity was observed, together with a significant trend in risk. A similar risk was observed for diversity within vegetables (RR, 0.6, highest versus lowers quartile), but no consistent association was found for fruit, meat and fish, and "other food" diversity. A similar pattern was observed when colon and rectal cancers were considered separately or across separate strata of sex and age. Diet diversity is related to a moderately decreased risk of colorectal cancer. These results add epidemiological support to the dietary guidelines recommending a more varied diet, and, if confirmed by other studies, would have considerable public health implications.