Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, has been implicated in cancer risk. In the present study we used a melting curve analysis to investigate the association of the common MTHFR C677T polymorphism with lymphoproliferative diseases. Patients (n = 117) were compared with age- and sex-matched control subjects (n = 154). Our results indicate that the 677T variant occurred less frequently in patients (26%) than in the control group (33.7%; P = 0.05). Investigation of the variant allele (677T) frequency in the subgroups with Hodgkin's lymphoma (HC) and B-cell neoplasms (BCNs) revealed that this difference was a result of the significantly lower distribution of the variant allele in patients with HL (20.5%; P=0.01). This was accompanied by a significantly higher frequency of the homozygote normal genotype (677CC) among the patients with HL. In patients with BCNs the distribution of the variant allele (30.3%) was comparable to that in the control group (P=0.47). However, the difference between HL (20.5%) and BCNs (30.3%) did not reach statistical significance (P=0.09). Our results suggest that the distribution of the C677T polymorphism may vary among lymphoproliferative diseases. J. Clin. Lab. Anal. 20:37-41, 2006. (c) 2006 Wiley-Liss, Inc.