The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism has been associated to a higher risk to develop proximal gastric cancer.To study the role of the MTHFR C677T polymorphism as a risk factor for the development of distal gastric cancer (DGC) in a Mexican population.Fifty-one histologically confirmed DGC (mean age = 57.6y, F:M = 0.76) and 83 ethnically matched non-GC controls (mean age 51.5y, F:M = 0.59) were studied. The MTHFR C677T polymorphism was typed by PCR-RFLP. The infection by Helicobacter pylori was defined by the positive result of at least two of the next diagnostic tests: histology, rapid urease test and culture.Among the GC patients, 16 (31.4%) were homozygous for C and 23 (45.1%) were CT Among the non-cancer control patients 17 (20.5%) were CC and 49 (59%) were CT. No difference was found in the frequency of the mutated variant MTHFR 677T between the GC cases and the non-cancer control patients (23.5% vs. 20.5 respectively) (p = 0.84; odds ratio: 1.19, 95% confidence interval: 0.48-2.98). The frequency of MTHFR 677TT genotype was not influenced by the infection by H. pylori.The mutated genotype TT of the MTHFR is frequent in Mexican population. Our study provides evidence that there is no association between the MTHFR C677T polymorphism and the development of gastric cancer in the Mexican population studied.