Introduction: Phospholipids are possible favorable agents for colorectal cancer (CRC). Choline has been inversely related to CRC risk but findings are inconsistent. Our study aimed to assess the effect of dietary sphingomyelin (SM) choline moiety and total choline on risk of CRC.Method: This analysis is based on a multicenter case–control study conducted between 1992 and 1996 in Italy. A total of 6107 subjects were enrolled, including 1225 colon cancer cases, 728 rectal cancer cases and 4154 hospital-based controls. We applied data on the composition of foods in terms of SM choline moiety and choline intake on dietary information collected through a validated food-frequency questionnaire. Odds ratio (OR) for energy-adjusted tertiles of SM choline moiety and choline were estimated through logistic regression models adjusted for sex, age, center, education, alcohol consumption, body mass index, family history of CRC, and physical activity.Results: Choline was inversely related to CRC risk (OR=0.85, 95% confidence interval [CI] 0.73-0.99). This association was consistent in colon and rectal cancer. SM choline moiety was not associated with CRC risk (OR=0.96, 95% CI 0.84-1.11).Conclusion: This study shows an inverse association between choline intake and CRC, while no association was found with SM choline moiety.