This study was designed to investigate the association of MTHFR C677T polymorphism and the risk of two common musculoskeletal sarcomas, osteosarcoma and chondrosarcoma. MTHFR genotypes were determined in 56 patients (44 osteosarcoma, 12 chondrosarcoma) and 44 controls using the PCR-RFLP technique. In the gender subgroup analysis, wild-type A allele frequency was higher in male osteosarcoma patients than in male control subjects (P = 0.064). Mutant V allele and mutant VV genotype were similar in the control group compared to the sarcoma groups (P > 0.05). No correlation could be proved between patient tumour site, presence of metastasis, and local tumour relapse and MTHFR polymorphism. The MTHFR C677T polymorphism may not be important in an individual's susceptibility to osteosarcoma and chondrosarcoma in Turkey and may not be a useful marker for identifying patients at high risk of developing sarcomas.