We present the case of a man who died 11 years after the onset of xanthoma disseminatum. His course was marked by numerous, large recurrent intracranial dural-based xanthomatous tumors requiring repeated neurosurgical intervention. Late in his course there was progressive quadriparesis, ataxia, ophthalmoplegia and bulbar palsy as a result of intraparenchymal brainstem involvement. At autopsy, there was extensive meningeal and intraparenchymal CNS disease and widespread systemic infiltrates. The gross and microscopic pathology are presented with immunohistochemical, ultrastructural and biochemical details. The present case is discussed in the context of the current classification scheme and the recent literature, where it is exceptional for the extent of CNS disease. Xanthoma disseminatum is currently classified as a non-X histiocytopathy, the pathogenesis of which remains uncertain. CNS involvement carries a poor prognosis in this otherwise benign condition.