Reported associations between genetic polymorphisms in folate-metabolizing enzymes and lymphoid malignancies suggest etiologic involvement of one-carbon metabolism and its related dietary exposures. We examined dietary factors of one-carbon metabolism in relation to non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) among 27,111 healthy male smokers who completed baseline dietary questionnaires in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. During a follow-up of up to 16.4 years (1985-2001), 195 NHL and 32 MM cases were ascertained. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). There was no significant association between dietary folate and NHL (HR comparing fourth to first quartile, 1.03; 95% CI, 0.68-1.55). Dietary vitamin B12 was inversely associated with NHL (HR, 0.61; 95% CI, 0.37-1.00; P(trend) = 0.06). The inverse association of vitamin B12 was evident for diffuse subtype but did not reach statistical significance. There were no significant associations of dietary vitamin B6 or B2, methionine, or alcohol with NHL. None of the dietary or supplemental one-carbon nutrients were associated with MM, although the power of these analyses was limited. Our results suggest that high intake of vitamin B12 among heavy smokers may be protective against NHL but warrant further studies, including among nonsmokers.