The relation between meal frequency and the risk of colorectal cancer was investigated in a case-control study conducted in North Italy on 889 cases of colon cancer, 581 cases of rectal cancer, and 2475 controls admitted to hospital for acute, nonneoplastic, or digestive disorders. As compared to individuals who reported 2 or fewer meals per day, the multivariate colon cancer odds ratios were 1.7 [95% confidence interval (95% CI), 1.5-2.1] for 3, and 1.9 (95% CI, 1.1-3.3) for 4 meals or more. Corresponding rectal cancer odds ratios were 1.4 (95% CI, 1.1-1.7) for 3, and 1.9 (95% CI, 1.1-3.5) for 4 meals or more. The direct trends in risk of colorectal cancer with frequency of eating were not substantially modified by allowance for various dietary and nondietary potential confounding factors, including an approximate measure of total energy intake, and did not show significant effect modification across strata of age, sex, education, and other major risk covariates. A role of meal frequency in the etiology of colorectal cancer is biologically plausible, since when a meal is eaten, the gallbladder contracts and releases bile acids. Thus, eating patterns can influence the enterohepatic circulation and, consequently, the exposure time of intestinal mucosa to bile acids.