An 11-yr-old Peron's tree frog (Litoria peronii) was presented with neurologic signs progressing from head bobbing to circling and incoordination. Postmortem and histologic evaluations demonstrated the presence of a cerebral xanthoma, a large cholesterol granuloma expanding the leptomeninges. The nodule in the cerebral cortex consisted of arrays of cholesterol clefts surrounded by foamy vacuolated macrophages. The factors leading to focal cerebral xanthomatosis are unclear, and the relationship between trauma, dietary lipid composition, hypercholesterolemia, and xanthomas in amphibians requires further investigation.