Gliosarcoma is a variant of glioblastoma (GBM) with both glial and mesenchymal differentiation. The genetic profile of gliosarcoma is similar to that of primary GBM, except for rare EGFR amplification. However, little is known about O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH) 1/2 mutations in gliosarcomas. The objective of this study was to investigate the status of MGMT methylation and IDH1/2 mutations, and to determine the effect of current treatment options for 26 patients with gliosarcoma. Among 26 cases, 21 were primary gliosarcomas, four secondary gliosarcomas, and one radiation-induced gliosarcoma. MGMT methylation was detected in three cases (11.5%), of which one was found in primary gliosarcoma and two in secondary gliosarcoma. IDH1 mutation was found in two cases (7.7%), of which one was in secondary gliosarcoma and the other in primary gliosarcoma with MGMT methylation. A case of primary gliosarcoma with both IDH1 mutation and MGMT methylation had a focal oligodendroglial component. No IDH2 mutation was found. Patients who underwent gross total resection (GTR) during first surgery had better survival (mean overall survival 18.1 vs. 9.04 months; P = 0.0543). In multivariate analysis, GTR and/or gamma knife surgery at recurrence was the independent favorable prognostic factor (P = 0.0003). In conclusion, MGMT methylation and IDH1 mutation are rare events in gliosarcomas, and only aggressive and repetitive local control seems to be effective in treatment of gliosarcoma.