The neuropathologic study of a 7-month-old female patient affected by familial erythrophagocytic lymphohistiocytosis (FEL) reveals three main features: (1) a lymphohistiocytic leptomeningitis with erythrophagocytosis; (2) perivascular lymphohistiocytic cuffs in the cerebral and cerebellar white matter and, to a lesser extent, in the thalamus, the reticular formation of the brain stem and the griseum pontis; (3) perifocal gliosis and demyelination, especially in the cerebellar white matter. The lesions remind of the perivenous post-infectious encephalomyelitides. Perifocal demyelination has been reported in FEL very seldom. Although its pathogenesis is not known, immune mechanisms could play a role by analogy with perivenous encephalomyelitis.