Summary. Lymphoproliferative diseases are characterized by chromosomal aberrations, and susceptibility may depend on inherited activity of enzymes required for DNA synthesis and methylation. We analysed genetic polymorphisms for methionine synthase (MS) A2756G, methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C in Caucasians with non-Hodgkin's lymphoma (NHL; n = 151), multiple myeloma (MM; n = 90) and 299 control subjects. The MS 2756 AG/GG genotypes were significantly under-represented in NHL (26·2%) vs control subjects (37·2%; P = 0·02), and conferred a 2·4-fold lower risk of follicular (odds ratio = 0·41, 95% confidence interval: 0·19–0·88, p = 0·02) but not diffuse large B-cell lymphoma. MM patients showed no significant difference in the polymorphisms compared with control subjects.