Background: Previous epidemiologic research suggests a protective role of one-carbon nutrients in carcinogenesis. Folate, however, may play a dual role in neoplasms development: protect early in carcinogenesis and promote carcinogenesis at a later stage. We prospectively examined associations between intake of total folate, methionine, riboflavin, vitamin B6, and risk of lymphoid and myeloid neoplasms (including subtypes) and investigated whether alcohol modified the effects of folate. Methods: The Netherlands Cohort Study consists of 120,852 individuals who completed a baseline questionnaire in 1986, including a 150-item food-frequency questionnaire. After 17.3 years of follow-up, 1,280 cases of lymphoid and 222 cases of myeloid neoplasms were available for analysis. Results: Intakes of folate, methionine, and riboflavin were not associated with lymphoid or myeloid neoplasms. For vitamin B6, a statistically significantly increased myeloid neoplasms risk was observed (highest vs. lowest quintile: HR = 1.87; 95% confidence intervals, 1.08-3.25). When analyzing by lymphoid and myeloid neoplasms subtypes, no clear associations were observed for most subtypes, with just a few increased risks for some subtypes and nutrients. Some risks became nonsignificant after excluding early cases. No interaction between alcohol and folate was observed. Conclusions: We observed a few significant positive associations; however, some of these would be expected to arise due to chance alone. Furthermore, some risks became nonsignificant after excluding early cases. Therefore, we conclude that there is no association between one-carbon nutrient intake and risk of lymphoid and myeloid neoplasms. Impact: This study contributes substantially to the limited and inconclusive evidence on the association with one-carbon nutrients.