Non-Alzheimer-type dementias occur in association with a variety of pathological conditions that include a group of diseases characterized by atrophy of the frontal and temporal lobes. Frontotemporal dementia (FTD) is a clinical entity that comprises at least two distinct diseases: Pick's disease with Pick bodies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). The vast majority of FTLD-U is now referred to as FTLD-TDP, following the recent discovery of TAR DNA-binding protein of 43 kDa (TDP-43) as the major constituent of the ubiquitin-positive inclusions. FTLD-TDP, but not Pick's disease with Pick bodies, is often associated with motor neuron disease (MND). MND is a group of diseases in which the central nervous system lesions were long believed to be confined to the motor neuron system. In other words, MND was not considered to be associated with other neurological symptoms such as dementia. Nevertheless, more than 200 FTD cases associated with clinical MND have been reported in Japan since 1964. Neuropathologically, MND in such FTD cases was essentially similar to MND in cases without dementia. The combination of FTD and MND was so characteristic that we considered these cases comprise a unique clinicopathological subgroup of FTD. FTD with MND and the classical MND without dementia share the occurrence of ubiquitinated TDP-43-positive inclusions, a finding that could be a key to unlock the pathological backgrounds of both diseases.