The methylenetetrahydrafolate reductase (MTHFR) enzyme may influence cancer development by affecting DNA methylation, synthesis and repair. The MTHFR 677C-->T single nucleotide polymorphism (SNP) has been associated with decreased enzyme activity and has therefore been implicated in cancer development. We analyzed the MTHFR 677C-->T SNP in 2,777 incident prostate cancer cases and 1,639 population controls from the CAncer Prostate in Sweden study (CAPS). No significant association was found overall between prostate cancer risk and the 677C-->T SNP (p = 0.27) with heterozygote (CT) and homozygote (TT) allele carriers showing ORs of 1.12 (95% CI: 0.98-1.27) and 1.02 (95% CI: 0.80-1.30), respectively. In the subgroup of low risk prostate cancer, heterozygote-but not homozygote-allele carriers displayed a slight over-risk with an OR of 1.21 (95% CI: 1.03-1.41). Among men under 65 years of age, the 677C-->T SNP was associated with prostate cancer risk (p = 0.007), with odds ratios of 1.33 (95% CI: 1.09-1.63) for heterozygote allele carriers and 0.86 (95% CI: 0.6-1.24) for homozygote allele carriers. However, this association was attributed to a shift in the genotype distribution in the young controls. In conclusion, our results do not provide strong support for the hypothesis that the MTHFR 677C-->T polymorphism is related to prostate cancer risk.