There are several studies published to assess the associations of murine double minute 2 (MDM2) genetic polymorphisms with risk of malignant bone tumors, but they reported contradictory results and failed to confirm a strong and consistent association. To assess the evidence regarding the associations of MDM2 genetic polymorphisms with the risk of malignant bone tumors, we conducted a meta-analysis of epidemiological studies. The pooled odds ratio (OR) with its 95% confidence intervals (95% CI) was used to assess these possible associations. Four studies with a total of 3,958 individuals were finally included the meta-analysis. Meta-analysis of two studies on MDM2 SNP309 polymorphism showed that MDM2 SNP309 polymorphism was associated with an increased risk of malignant bone tumors (G versus T: OR = 1.72, 95% CI 1.35-2.20, P < 0.001; GG versus TT: OR = 2.64, 95% CI 1.59-4.39, P < 0.001; GG/GT versus TT: OR = 1.87, 95% CI 1.33-2.62, P < 0.001; GG versus TT/GT: OR = 2.20, 95% CI 1.38-3.51, P = 0.001). Meta-analysis of those two studies on MDM2 rs1690916 polymorphism showed that MDM2 rs1690916 minor allele A was associated with decreased risk of malignant bone tumors (OR = 0.60, 95% CI 0.46-0.77, P < 0.001). Meta-analyses of available data show that there are significant associations of MDM2 SNP309 polymorphism and MDM2 rs1690916 polymorphism with malignant bone tumors.