A 10-yr-old female lion (Panthera leo) presented for acute onset ataxia and weakness with a history of two seizure episodes 6 mo prior to presentation and a persistent head tilt for at least 6 mo. Gross necropsy findings included a gelatinous mass in the right cerebral hemisphere extending from the frontal to the occipital lobes. Histologically, the mass was composed of polygonal cells surrounding lakes of mucinous material. These cells had clear cytoplasm, ovoid basophilic nuclei, and inapparent cell processes. Immunoreactivity was positive for S100 and neuron-specific enolase but negative for glial fibrillary acid protein, myelin basic protein, neurofilament triplet, vimentin, and cytokeratin. All findings were consistent with an oligodendroglioma. A second neoplasm, a pulmonary adenoma, was also identified at necropsy.