Brain abnormalities were described in a patient who had experienced Sjögren-Larsson syndrome (SLS) with typical clinical signs. Examination of the brain revealed (1) accumulation of peculiar lipoid substances stained lightly with periodic acid-Schiff (PAS) in the subpial, subependymal, and perivascular glial layers, the subpial and perivascular spaces, and the white matter of the cerebrum and brainstem; (2) proliferation of perivascular macrophages containing lipofuscin-like pigments; (3) dense distribution of round or ellipsoid small bodies stained strongly with PAS in the subpial, subependymal, and perivascular glial layers and the white matter; (4) appearance of spheroid bodies in the neuropil of relay nuclei (the lateral geniculate body, pontine nuclei, inferior olivary nucleus, posterior funicular nucleus, and dentate nucleus) and the white matter; and (5) reduction of myelinated nerve fibers in the cerebral and cerebellar white matter. Six-layered neuronal cytoarchitecture was preserved in the cerebral neocortex, except for the insula where pyramidal neurons were arranged at random. The exact mechanisms remain unclear, but it is suggested that peculiar lipoid substances may accumulate in the specific regions of the brain and that neuronal and astrocytic processes may be primarily affected in SLS.