The Fc receptor-like 3 (FCRL3) -169 C/T polymorphism has been reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but with inconsistent results. The aim of this study was to explore whether the FCRL3 -169 C/T polymorphism confers susceptibility to RA and SLE. The authors conducted a random effect meta-analysis on the associations between the C/C (recessive effect) or C/C + C/T (dominant effect) genotype or the allele C of the FCRL3 -169 polymorphisms and RA or SLE in different populations. In total, 15 separate comparisons, 12 for RA and 3 for SLE, drawn from nine European and six Asian population samples were included in this meta-analysis. No association between RA and the FCRL3 C allele was found for all study subjects (OR = 1.064, 95% CI = 0.987-1.146, p = 0.107). However, stratification by ethnicity indicated that the FCRL3 C allele was significantly associated with RA in Asians (OR = 1.203, 95% CI = 1.097-31.319, p < 0.001). Conversely, no association was detected for this allele and RA in Europeans (OR = 0.997, 95% CI = 0.931-1.068, p = 0.933). The ORs for the C/C + C/T and C/C genotypes in these ethnic groups showed the same trends as the FCRL3 C allele. An association between SLE and the FCRL3 -169 A allele was found in all study subjects (OR = 1.115, 95% CI = 1.003-1.240, p = 0.043), but meta-analysis excluding studies with controls not in HWE did not show the association. This meta-analysis suggests that the FCRL3 -169 C/T polymorphism is a significant risk factor for RA in Asians, but not in Europeans.