Motor neuron disease (MND) may be complicated by frontotemporal dementia and/or an extrapyramidal movement disorder. Several studies have identified the pathological substrate for dementia in MND as being ubiquitin-immunoreactive inclusions and dystrophic neurites in the extramotor neocortex and hippocampus. Although degenerative changes have previously been noted in the basal ganglia and substantia nigra in MND, detailed pathological studies with clinical correlation are lacking. We examined postmortem material from eight patients with a history of MND and dementia, four of whom also had prominent extrapyramidal features. All cases showed the expected degenerative changes in the pyramidal motor system and ubiquitin-positive inclusions in the extramotor cortex. In addition, the cases with a history of extrapyramidal features had striking pathology in the basal ganglia and substantia nigra; neuronal loss and gliosis ranged from moderate to severe and immunohistochemistry demonstrated numerous neuronal inclusions and dystrophic neurites, which were reactive for ubiquitin, but not tau or alpha-synuclein. Similar pathology was either absent or much milder in cases without extrapyramidal features. This study illustrates the utility of ubiquitin immunohistochemistry in demonstrating the range of pathology in MND and provides a neuropathological correlate for the extrapyramidal features which may occur in MND with dementia.