Epidemiologic studies have suggested that high alcohol and low folate intakes might be jointly associated with colorectal tumors via DNA metabolism. We investigated this hypothesis in a case-control study comparing small adenoma (< 10 mm, n = 154), large adenoma (n = 208), and polyp-free (n = 426) subjects, recruited after colonoscopy, and cancer cases (n = 171) with population controls (n = 309). Odds ratios for the fifth vs. the first quintile of intake (OR5) were as follows: Folate intake was related to the risk of small and large adenomas compared with polyp-free subjects [OR5 = 0.5, 95% confidence interval (CI) 0.3-1.0; OR5 = 0.5, 95% CI 0.3-1.0, respectively], whereas alcohol was related to risk of large adenomas (OR5 = 4.1, 95% CI 2.1-8.1), but not of small adenomas (OR5 = 1.2, 95% CI 0.7-2.2). In large adenomas, there was some interaction between alcohol and folate, with a stronger protective effect of folate with high alcohol intake and a stronger risk with alcohol with low folate intake. For cancer patients compared with general population controls, neither alcohol (OR5 = 1.6, 95% CI 0.8-3.0) nor folates (OR5 = 1.0, 95% CI 0.5-2.0) were related to risk. Our data support the hypothesis that folate intake might be mostly beneficial to prevent adenoma formation but might have an additional protective effect against adenoma growth associated with alcohol.