Methylentetrahydrofolate reductase C677T genotype was assessed in 35 patients of both sexes aged between 3.2 and 5.4 years affected by Wilms tumor (WT) and in 70 random controls. Statistical analysis was performed comparing frequency of WT methylentetrahydrofolate reductase genotypes with 70 controls and a larger Italian population. The homozygous TT and heterozygous CT genotypes were associated with a significantly higher frequency of WT than CC genotype. By reducing tissue folate concentrations and inducing hypomethylation both TT and CT genotypes could be risk factors for WT (odds ratio >1).