Epidemiological studies have investigated the association between HER2 codon 655 polymorphism and breast cancer susceptibility. However, the results are still inconclusive. To obtain a more precise estimation of the relationship, this meta-analysis was performed. A total of 22 studies including 9,209 cases and 10,132 controls were collected. The strength of association between HER2 codon 655 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 22 studies were pooled into the meta-analysis, there was no evidence for significant association between HER2 codon 655 polymorphism and breast cancer susceptibility (for Val/Ile vs. Ile/Ile: OR = 1.069, 95% CI = 0.976-1.172; for Val/Val vs. Ile/Ile: OR = 1.191, 95% CI = 0.922-1.538; for dominant model: OR = 1.093, 95% CI = 0.991-1.206; for recessive model: OR = 1.141, 95% CI = 0.902-1.444). In the subgroup analysis by the source of controls and ethnicity, no significant increased risk was found in all genetic models. However, the current results indicated the modest association between the HER2 Ile655Val polymorphism and Asian population (Val/Ile vs. Ile/Ile: OR = 1.207, CI = 1.006-1.450). In summary, the meta-analysis suggests that HER2 codon 655 polymorphism is not associated with the increased breast cancer risk.