OBJECTIVE: To present the case of a man with progressive speech loss and other clinical features and diagnostic tests consistent with fronto-temporal dementia but whose postmortem neuropathologic findings revealed Alzheimer disease (AD). BACKGROUND: Progressive apraxia of speech presents without true language abnormalities, usually seen with frontal lesions and not associated with AD pathology. METHOD: We describe the clinico-pathologic case of an 87-year-old man with progressive loss of speech function and present the prospective presentation of his syndrome using structural (magnetic resonance imaging) and metabolic (positron emission tomography) neuro-imaging studies, neuropsychologic testing, and pathology. RESULTS: His syndrome was characterized over the first 6 to 9 years by progressive deterioration of speech production, alteration of mood, and dysphagia but near normal language, memory, and visual-spatial function. At 8 years, fluorodeoxyglucose-positron emission tomography showed largely frontal metabolic abnormality. Over his final 11/2 years, he was mute and withdrawn. Neuropathologic findings showed neuritic plaques and neurofibrillary tangles, but no signs of frontotemporal dementias such as Pick bodies or ubiquitinated tau-negative inclusions. CONCLUSIONS: There can be overlap in the presentation of fronto-temporal dementia and AD despite the disparate pathologic bases of the underlying diseases. It has yet to be determined how to differentiate these diseases in such variant presentations and whether such atypical AD syndromes are equally amenable to standard therapies for AD. © 2007 Lippincott Williams & Wilkins, Inc.