Previous work examining the cortical-subcortical distinction as it relates to cognitive patterns has not typically used genetic confirmation to identify these groups, controlled for age, or used a comprehensive battery to assess specific cognitive abilities. The present study is the first to include only genetically confirmed Familial Alzheimer's disease (FAD) and Huntington's disease (HD) patients to evaluate this distinction. Ten patients with FAD, 11 patients with HD, and 17 matched healthy individuals were compared on a comprehensive neuropsychological battery that included tasks of language, memory, attention, visual-spatial, and executive function. The only neuropsychological measures to differentiate the two clinical groups were Animal Fluency and Letter Fluency; performance on all other measures did not differ. Although the neuropsychological battery adequately distinguished between clinical and healthy individuals, it was not useful to further differentiate the cortical or subcortical nature of the disease. FAD and HD appear to have similar neuropsychological profiles; therefore the cortical versus subcortical cognitive distinction may not be clinically meaningful.