Two oligodendrogliomas in two domestic cats involved mainly the rostral brain stem, midbrain, fourth ventricle, and cerebellum. Both cats were aged neutered males presenting with clinical neurologic deficits suggestive of a brain stem lesion. Magnetic resonance imaging of both tumors demonstrated lesions with a pattern of heterogeneous contrast enhancement and multifocal lesions in one cat. Routine cerebrospinal fluid analysis was normal in one cat and suggestive of an inflammatory disease in the other. Oligodendroglioma cells were seen in cytospin preparations of cerebrospinal fluid from both cats. In each cat, the tumors occurred intraventricularly in the midbrain and fourth ventricle with aggressive intraparenchymal infiltration. There was extensive growth into the basilar subarachnoid space of the midbrain and brain stem in one cat. One tumor was well differentiated, and the other was an anaplastic subtype. Immunostaining for several myelin- and oligodendroglia-specific antigens was negative with formalin-fixed tumors and with unfixed frozen samples from one cat. In both tumors, component cells of the intratumoral vascular proliferations were positive for human von Willebrand factor VIII antigen or smooth muscle actin. Immunocytochemical reactivity for glial fibrillary acidic protein identified both reactive astrocytes and a subpopulation of minigemistocytes in both tumors. Ultrastructurally, the tumor cells were unremarkable except for their prominent desmosomal junctions and paucity of microtubules.