Seven cases of mixed glioblastoma multiforme (GBM) and sarcoma, or gliosarcoma (GS) and six cases of GBM with a prominent pilocytic or spindle cell component were studied with a panel of ten antibodies using the ABC method. All 13 cases were originally diagnosed as GS based on hematoxylin and eosin- (H&E) and reticulin-stained sections. In all GS, the glial component stained strongly for glial fibrillary acidic protein (GFAP), and most stained for S-100 protein, while the sarcomatous areas of GS did not stain for either of these antigens. This resulted in a characteristic, bimorphic marmorate staining pattern. In contrast, spindled GBM stained diffusely for GFAP and S-100 protein. Vimentin was detected in neoplastic glia of both GBM and GS and in the sarcomatous foci of GS. A spectrum of cytokeratins, Factor VIII, desmin and neurofilament were not detected in either GS or GBM. Actin, Leu 7 and alpha-1-antichymotrypsin were focally and inconsistently found in both GS and GBM. Perithelial spindle cell proliferations and intramural spindle cells within thick-walled vessels stained for GFAP, S-100 protein and/or vimentin. These studies confirm that GS is a true biphasic neoplasm that frequently cannot be distinguished from pilocytic or spindled GBM on routine histologic examination. Invasion of the dura, leptomeninges, and hyperplastic or hypertrophied blood vessels by malignant glial cells particularly confounds interpretation of H&E and reticulin stains. Immunohistochemical staining for GFAP complements the reticulin stain in confirming the presence of two cell populations in GS.