The cellular origin of the sarcomatous component of gliosarcomas is controversial. It is not clear if the sarcoma arises in transition from the glial cells that comprise the gliomatous component or independently arises from non-neoplastic mesenchymal cells of the tumor stroma. Using comparative genomic hybridization (CGH) along with cytogenetic analysis, fluorescence in situ hybridization (FISH) analysis, and polymerase chain reaction (PCR) analysis of microsatellite allelic imbalance, we have evaluated the genetic alterations in the gliomatous and sarcomatous components of five gliosarcomas. The glial element was grade 4 fibrillary astrocytoma (glioblastoma multiforme) in all five tumors. The sarcoma elements were fibroblastic without osseous, chondroid, or angiosarcomatous differentiation. Gain of chromosome 7, loss of chromosome 10, deletions of the chromosome 9 p-arm, and alterations of chromosome 3 were frequently observed, demonstrating that gliosarcomas can be genetically classified as belonging to the spectrum of glioblastomas. Furthermore, the sarcomatous and gliomatous portions of each gliosarcoma investigated were similar with respect to both the presence and absence of specific genetic alterations. This observation supports the hypothesis that the sarcomatous component of a gliosarcoma either arises from the same common precursor cell as the gliomatous portion, or it arises from the gliomatous portion itself.