Background:The simultaneous occurrence of multiple intracranial neoplasms has been reported, especially in genetic familial syndromes and after cranial irradiation. In the absence of these etiologic factors, some reports showed simultaneous occurrence of glioblastoma and meningioma but the association between gliosarcoma and meningioma is unknown.Case Description:We report a case of a 51-year-old woman with synchronous gliosarcoma and meningioma in whom extensive immunohistochemical characterization and molecular profile was performed. The gliosarcoma recurred 21 months after the first resection, reaching 3 years of overall survival. A molecular characterization of all three lesions was performed. None of the lesions showed the presence of mutations in TP53 and BRAF genes. MGMT analysis showed the presence of loss of expression associated with promoter hypermethylation in both gliosarcoma lesions. EGFR overexpression and gene amplification was found only in the recurrent gliosarcoma.Conclusion:The immunohistochemistry and molecular data of this unique case, suggest the distinct clonal origin of meningioma and gliosarcoma lesions, and the association of MGMT methylation with the presumable favorable prognosis observed.