The clinicopathological features of Nasu–Hakola disease are described by reviewing previously reported cases and adding consideration to newly disclosed evidence. This disease is an autosomal recessive disorder characterized by membranocystic lipodystrophy in the skeletal system and sclerosing leukoencephalopathy in the nervous system. The leukoencephalopathic alterations are demyelinization of the cerebral white matter, associated with conspicuous fibrillary gliosis and preservation of the subcortical arcuate fibers. Sudanophilic granules are focally scattered in the perivascular space or widely infiltrated in the affected white matter, and some neuronal loss with deposits of calcospherites is encountered in the basal ganglia and also in the thalamus. Spheroid formation with an increased number of neurofilaments in the neuronal axon is considered a possible pathogenesis, and a primary vascular mechanism is also suggested. Interestingly, most of the reported cases of Nasu–Hakola disease are from Japan and Finland which suggests heredofamilial background as a cause.