ALS is a multisystem disorder affecting motor and cognitive functions. Bulbar-onset ALS (bALS) may be preferentially associated with cognitive and language impairments, compared with spinal-onset ALS (sALS), stemming from a potentially unique neuropathology. The objective of this systematic review was to compare neuropathology findings reported for bALS and sALS subtypes in studies of cadaveric brains. Using Cochrane guidelines, we reviewed articles in MEDLINE, Embase, and PsycINFO databases using standardized search terms for ALS and neuropathology, from inception until July 16th 2016. 17 studies were accepted for analysis. The analysis revealed that both subtypes presented with involvement in motor and frontotemporal cortices, deep cortical structures, and cerebellum and were characterized by neuronal loss, spongiosis, myelin pallor, and ubiquitin+ and TDP43+ inclusion bodies. Changes in Broca and Wernicke areas – regions associated with speech and language processing – were noted exclusively in bALS. Further, some bALS cases presented with atypical pathology such as neurofibrillary tangles and basophilic inclusions, which were not found in sALS cases. Given the limited number of studies, all with methodological biases, further work is required to better understand neuropathology of ALS subtypes.