A case of cerebral xanthomatosis is described in a long-nosed snake (Rhinocheilus lecontei). A 13-year-old long-nosed snake presented for pronounced lethargy, anorexia, and diminished righting reflex. The snake failed to respond to medical therapy and was euthanized. On histology, a focal cerebral cholesterol granuloma (xanthoma) was found within the lateral ventricle causing mild hydrocephalus, marked compression atrophy of the overlying dorsal cortex, and mild compression and disorganization of the ventral nucleus sphericus. Xanthomatosis is believed to be the cause of the neurological signs and the ultimate lack of response to medical therapy in this case. This case demonstrates another differential for neurologic dysfunction in snakes.