To date, many publications discussed the correlation between ERCC2 Asp312Asn polymorphism and breast cancer risk. However, the results were not unanimous. In order to derive a more precise conclusion, a meta-analysis was performed in this study by searching Medline, PubMed, and ISI Web of Knowledge databases. Finally, 17 studies including 12,019 cases and 10,747 controls were collected for this meta-analysis. The strength of association between ERCC2 Asp312Asn polymorphism and breast cancer risk was assessed by calculating crude ORs with 95% CIs. Overall, no significant associations between ERCC2 Asp312Asn polymorphism and breast cancer susceptibility were found. In the stratified analysis by ethnicity, significant associations were observed for Asn/Asn versus Asp/Asp (OR = 0.55; 95% CI 0.32-0.96) and Asn/Asn versus Asn/Asp + Asp/Asp (OR = 0.53; 95% CI 0.32-0.90) in Asians. In the stratified analysis by study design, significant associations were found for Asn/Asn versus Asp/Asp (OR = 0.79; 95% CI 0.64-0.98) and Asn/Asn versus Asn/Asp + Asp/Asp (OR = 0.82; 95% CI 0.68-0.99) in population-based studies. In conclusion, this meta-analysis provides an evidence that ERCC2 312Asn allele may have a protective effect for breast cancer development in Asians.