TDP-43 is a major component of ubiquitin-positive, tau-negative inclusions in amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration. We immunohistochemically examined the neostriatum from 14 cases of classic ALS (cALS), six cases of ALS with dementia (ALS-D), and 20 control subjects. TDP-43-positive, crescent or circular inclusions were found in neostriatal small neurons in 19 of 20 cases of ALS, but not in controls. Two types of inclusions were found in the large neurons: ubiquitin-positive, TDP-43-negative rod-like inclusions, and ubiquitin- and TDP-43-positive pleomorphic inclusions. The latter were specific to ALS; they were found in seven cases of cALS and in all of ALS-D. TDP-43-positive glial inclusions were also found in 12 cases of cALS and in all of ALS-D. These TDP-43-positive neuronal and glial inclusions were more numerous in ALS-D than cALS. In ALS-D, neuronal loss in the substantia nigra was found in all the cases, whereas mild gliosis without obvious neuronal loss was noted in the neostriaum in only two cases. These findings suggest that the neostriatum is also involved in the disease process of ALS with and without dementia.