P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83-1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82-0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80-0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80-0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78-0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78-0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.