Recently, Nishihira et al. demonstrated the presence of two types of TDP-43 pathology in sporadic amyotrophic lateral sclerosis (ALS) (Acta Neuropathol 2008; 116: 169–182). Type 1 represents the TDP-43 distribution pattern observed in classic ALS, whereas type 2 shows the presence of TDP-43 inclusions in the frontotemporal cortex, hippocampal formation, neostriatum and substantia nigra and is significantly associated with dementia. However, ALS with pallido-nigro-luysian degeneration (PNLD) is very rare. We recently encountered a case of ALS with PNLD of 9 years duration, in which the patient received artificial respiratory support for 6 years. In our case, neuronal loss and TDP-43-positive neuronal cytoplasmic inclusions were found in the globus pallidus, substantia nigra and subthalamic nucleus. Neither neuronal loss nor TDP-43-immunoreactive inclusions were found in the frontotemporal cortex and hippocampus. These findings suggest that the pallido-nigro-luysian system is also involved in the disease process of ALS and that ALS with PNLD is different from ALS with dementia based on the distribution pattern of neuronal loss and TDP-43 accumulation.