BACKGROUND: Food diversity has been recommended to achieve a healthy diet and prevent cancer. The relation between diet diversity and the risk of colorectal cancer was investigated using data from a multicenter case-control study carried out between 1992 and 1996 in Italy. METHODS: The study included 1225 subjects with cancer of the colon (688 men and 537 women), 728 with cancer of the rectum (437 men and 291 women), and 4154 controls (2073 men and 2081 women) residing in the same geographical areas. Odds ratios (ORs) of colon and rectal cancer and the corresponding 95% confidence intervals (CI) according to food diversity were derived from unconditional multiple logistic regression equations. RESULTS: For colon cancer, an inverse association for total diversity was found in males (adjusted OR of 0.65 for the highest vs the lowest quintile of total diversity; 95% CI: 0.46-0.93) and in females (OR = 0.85; 95% CI: 0.57-1.26). With respect to specific food groups, there was an inverse association only with diversity within vegetables (OR = 0.66; 95% CI: 0.54-0.81 in colon cancer and OR = 0.71; 95% CI: 0.55-0.91 in rectal cancer). CONCLUSIONS: This study suggests that total diversity is moderately related to a decreased risk of colorectal cancer risk. A better understanding of the potential influence of dietary patterns on colorectal cancer is needed.