Bunina body is known to occur in cases of sporadic amyotrophic lateral sclerosis (ALS), ALS with dementia (a so-called Mitsuyama type), and Guamanian ALS, and seems to lend a diagnostic priority to the presence of Bunina bodies. Absence of Bunina body in a subset of familial ALS with posterior column and spinocerebellar tract involvement or motor neuron disease with basophilic inclusion also adds credence to the specificity of Bunina body in ALS. However, despite its bright eosinophilia, distinct expression of cystatin C, and conspicuous ultrastructure, the origin of Bunina body is still unknown and remain several unsolved problems. Bunina bodies are usually seen within the cytoplasm or dendrites of degenerated and/or sometimes normal-looking large neurons. However, so far, no Bunina body has been found within the axoplasm. Bunina bodies are mainly distributed in the lower motor neurons. Only a single report described it in the Betz cell. Furthermore, several recent studies have revealed the occurrence in neurons which are so far considered to be exempt from the pathology of ALS, i.e. the oculomotor nucleus, Onufurowicz's nucleus, Clarke's nucleus, reticular formation of the brain stem, and subthalamic nucleus. In addition to the occurrence in neurons other than motor neurons, ultrastructurally similar or identical inclusions are reported in neurons of aged rats, the olfactory bulb of aged human, the spinal cord of a patient without ALS, and gangliocytoma. Bunina body probably represents a facet of the degenerating process of a neuron. A high incidence in ALS, particularly in lower motor neurons, awaits a further study of the pathogenesis of Bunina body.