This study was designed to investigate, in the Turkish population, an association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer. Our study was carried out in 35 patients with gastric cancer (20 men, 15 women) and 144 controls (75 men, 69 women) and 52 colorectal cancer (31 men, 21 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in cases versus controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 14.3% of gastric cancer versus 10.4% of controls. MTHFR C677T frequencies of the CC, CT and TT genotypes among colorectal cancer patients were 34.6%, 51.9% and 13.5%, respectively. MTHFR C677T polymorphism may not be important in an individual's susceptibility to gastric and colorectal cancer in Turkey and may not be a useful marker for identifying patients at high risk of developing gastric and colorectal cancer. Copyright (C) 2006 John Wiley & Sons, Ltd.