One-carbon metabolism is a network of biological reactions that plays critical role in DNA methylation and DNA synthesis, and in turn, facilitates the cross-talk between genetic and epigenetic processes. Genetic polymorphisms and supplies of cofactors (e.g. folate, vitamins B) involved in this pathway have been shown to influence cancer risk and even survival. In this review, we summarized the epi- demiological evidence for one-carbon metabolism, from both genetics and lifestyle aspects, in relation to breast cancer risk. We also dis- cussed this pathway in relation to breast cancer survival and the modulation of one-carbon polymorphism in chemotherapy. Emerging evidence on modulation of DNA methylation by one-carbon metabolism suggests that disruption of epigenome might have been the un- derlying mechanism. More results are expected and will be translated to guidance to the general population for disease prevention as well as to clinicians for treatment and management of the disease.