PURPOSE: Apolipoprotein E (APOE, MIM: 107741) has three functionally distinct isoforms of the protein (E2, E3, and E4), encoded by corresponding alleles epsilon2, epsilon3, and epsilon4, which have been well described. Findings from previous studies investigating association between APOE polymorphisms and breast cancer risk have been inconsistent. The present meta-analysis was conducted in order to investigate association of APOE polymorphisms with risk of breast cancer. MATERIALS AND METHODS: Several electronic databases were used for identification of studies containing information on APOE polymorphisms and breast cancer risk published up to January 2012. We identified 10 eligible studies, including 3,835 subjects (2008 patients, and 1,827 healthy controls), that reported on polymorphisms of APOE and risk of breast cancer. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using a fixed and random-effects models. RESULTS: Among studies reported from Asia, an association of the epsilon4 allele with increased risk of breast cancer, in comparison with the epsilon3 allele, was observed (OR, 1.56; 95% CI, 1.19 to 2.04; p=0.001). It should be noted that allele epsilon2 showed no association with breast cancer risk. Among Caucasians, neither the epsilon4 (OR, 0.99; 95% CI, 0.83 to 1.17; p=0.917) nor the epsilon2 (OR, 0.92; 95% CI, 0.72 to 1.17; p=0.514) allele showed an association with susceptibility to breast cancer, when compared with the epsilon3 allele. Carriers of the epsilon4 allele (E4E4, E4E3, and E4E2 genotypes), in comparison with the E3E3 genotype, showed an association with elevated risk of breast cancer only among Asians (OR, 1.75; 95% CI, 1.23 to 2.47; p=0.002). No publication bias was detected. CONCLUSION: This meta-analysis suggest that the APOEepsilon4 allele is a low-penetrant risk factor for development of breast cancer.