Methionine synthase reductase (MTRR) is one of the important enzymes involved in the folate metabolic pathway and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains inconclusive. For better understanding the effect of MTRR A66G polymorphism on breast cancer risk, a meta-analysis was performed. By searching PubMed and EMBASE, a total of six case-control studies, containing 6,084 cases and 6,756 controls, were included. The strength of association between MTRR A66G polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The results strongly suggested that there was no significant association between MTRR A66G polymorphism and breast cancer susceptibility in overall comparisons in all genetic models (additive model: OR 1.00, 95% CI 0.89-1.11, P = 0.943; dominant model: OR 1.00, 95% CI 0.91-1.10, P = 0.989; recessive model: OR 1.00, 95% CI 0.91-1.09, P = 0.926). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian and mixed population) and folate intake status (high and low folate intake), the results were negative. Sensitivity analysis demonstrated that omitting any study did not perturb the results. In conclusion, this meta-analysis strongly suggests that MTRR A66G polymorphism is not associated with breast cancer risk, especially in Caucasians and Asians.