Purpose: Single nucleotide polymorphisms (SNPs) in the mitochondrial DNA displacement-loop (D-loop) region have been reported to be associated with cancer risk and disease outcome in several types of cancer. In this study, we investigated whether the SNPs in mitochondrial D-loop were associated with the outcome of malignant fibrous histiocytoma (MFH). Experimental design: The D-loop region of mtDNA was sequenced for 80 MFH patients. The 3 years survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method. Results: The SNP sites of nucleotides 152T/C, 16,390G/A, 16,290C/T, 16,304T/C and the AC deletion at sites 523 and 524 were identified for prediction of post-operational survival by the log-rank test. In an overall multivariate analysis, the 16,290 and 16,390 alleles were identified as independent predictors of MFH outcome. The length of survival for patients with the rare allele 16,390A genotype was significantly shorter than that for patients with the frequent allele 16,390Gat the site 16,390. The same was seen for the rare allele 16,290T genotype when compared with matched allele 16,290C at the site 16,290 in MFH patients. Conclusions: These results suggested that SNPs in the D-loop are independent prognostic markers for patients with MFH. The analysis of genetic polymorphisms in the D-loop can help identify patient subgroups at higher risk of a poor disease outcome.