Although the pathological hallmarks of Alzheimer's disease (AD) and frontal variant frontotemporal dementia (fvFTD) predict different cognitive patterns, many comparative neuropsychological studies showed no difference in the expected cognitive domains. Inconsistencies in diagnostic criteria, small cohorts of patients, and neuropsychological assessment may account for such findings. Moreover, discrepancies in memory and executive dysfunctions that are expected to distinguish AD and fvFTD may reflect the basic brain organization. Adhering to a strict concordance of clinical and neuroradiological criteria, we compared many patients with AD and fvFTD using a large neuropsychological battery. One hundred and thirty-nine patients with AD (n=89) or fvFTD (n=50) were retrospectively considered in order to verify the diagnostic congruence of clinical and neuroradiological aspects. On this basis, 117 patients with AD (n=77) or fvFTD (n=40) with similar duration and severity of dementia were selected. Ninety-one healthy subjects were also controlled. Mean scores in tests for abstract reasoning, planning, set shifting, initiative, verbal fluency, immediate and episodic memory, constructive, ideomotor and orofacial praxis, selective and divided attention, visuomotor coordination, and visual perception were evaluated. Separate analyses of variance and post hoc Bonferroni tests showed that, with respect to controls, both patient groups were significantly impaired in all neuropsychological tests. Compared to fvFTD patients, AD patients were significantly impaired in episodic memory, selective attention, visual perception, visuomotor coordination, and constructive praxis, whereas no differences were found in executive, intellective, and linguistic abilities between the two patient groups. Logistic regression analyses revealed that episodic memory significantly predicted the diagnosis of AD while no executive deficit was able to predict the diagnosis of fvFTD. To conclude, memory, attention, and visuoconstructive deficits may distinguish AD with respect to fvFTD, in accordance with the severe temporo-parietal-occipital degeneration characterizing AD, but no executive impairment is consistently able to identify a relative compromise in fvFTD. Executive functions impairments possibly reflect the altered spatial-temporal integration of the frontal lobes with different brain areas, which prevents a clear-cut cognitive-brain correlation.