Cerebral atrophy often coexists with other brain disorders and by itself may alter the pattern of cerebral perfusion. If unrecognized, it may confound diagnoses based on brain single-photon emission tomography (SPET). In this retrospective study, we describe and evaluate criteria for the diagnosis of cerebral atrophy on technetium-99m hexamethylpropylene amine oxime brain SPET studies. The SPET scans of 11 patients with cerebral atrophy and ten controls were evaluated for the presence of a prominent interhemispheric fissure, presence of prominent cerebral sulci, separation of thalamic nuclei, and pronounced separation of caudate nuclei. The SPET studies were interpreted by two independent observers blind to the findings of magnetic resonance imaging, which provided the final diagnosis of cerebral atrophy. The combination of the four scintigraphic signs was accurate in the diagnosis of cerebral atrophy in 95% of the cases and had a sensitivity of 91% and a specificity of 100%.