Folate is crucial for normal DNA methylation, synthesis and repair, and deficiency of this nutrient is hypothesized to lead to cancer through disruption of these processes. There is some evidence to suggest that relatively high dietary folate intake might be associated with reduced colorectal cancer risk, especially among individuals with low methionine intake. A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993, a total of 389 women were diagnosed with colorectal cancer, identified by linkage to the Canadian Cancer Database. For comparative purposes, a subcohort of 5,681 women was randomly selected from the full dietary cohort at baseline. After exclusions for various reasons, the analyses were based on 295 cases and 5,334 non-cases. Folate intake was inversely associated with colorectal cancer risk (IRR = 0.6, 95% CI = 0.4–1.1, p for trend = 0.25). The inverse association was essentially similar among individuals with low and high methionine intake, and was similar for colon and rectal cancers when those endpoints were analyzed separately. Among individuals with low methionine intake, folate intake did not appear to lower the risk of rectal cancer, a finding that may be due, in part, to the low number of cases in the subgroup analysis. Overall, our data lend some support to the hypothesis that high folate intake is associated with a reduced risk of colorectal cancer. © 2001 Wiley-Liss, Inc.