Aberrant DNA methylation of CpG islands is a common epigenetic alteration found in cancers. DNA methylation is typically mediated by DNA methyltransferases (DNMTs). Only two studies have evaluated DNMT-1 and/or DNMT-3B gene polymorphisms in relation to breast cancer risk, and results have been inconsistent. We comprehensively evaluated genetic variations in the DNMT-1 and DNMT-3B genes with breast cancer risk among the participants of the Shanghai Breast Cancer Study, a large-scale, two-stage, case-control study. Of the 25 SNPs in the DNMT-1 and DNMT-3B genes analyzed, only one (rs8101866) reached a normal significance level (P = 0.042). This association, however, was no longer statistically significant after adjustment for multiple comparisons. Our data suggest that there is no apparent association of common DNMT-1 and DNMT-3B polymorphisms with the risk of breast cancer among Chinese women.