The folate availability seems to be critical for the DNA integrity since it is required for the transfer of methyl groups in the biosynthesis of thymidilate. Although the excessive incorporation of uracils to the DNA can be efficiently removed, this mechanism of reparation produces many double-strand breaks from two opposing nicks. Several chromosomal abnormalities (mainly translocations and deletions perhaps not well understood) are involved in the origin of lymphoproliferative disorders. The TT homozygosity at nucleotide 677 in the gene of methylene tetrahydrofolatereductase (MTHFR), a key enzyme in folate metabolism, was recently linked to a significant protection against colon carcinoma and acute lymphoblastic leukaemia in adults. We analysed the genotype frequencies of C677T-MTHFR in a group of 143 patients with lymphoproliferative disorders (REAL classification) and 200 controls. Overally, the frequencies of the polymorphic allele were similar (35.3% and 32.0% respectively)(P=0.6). We did not find differences between patients and controls except for myeloma/plasmacytoma group (n=26) which showed a CC genotype less than expected (19% vs 46%) (p=0.01) with a frequency ratio of 0.28 (0.10-0.77). Even among the IgG myeloma cases only one patient showed a common genotype (CC) (1/15, 7%) (P=0.003). If these preliminary data are validated with prospective studies, the 677C allele of MTHFR gene could be confirmed as an effective multiple myeloma protective factor (specially for the IgG cases).