Amyloid imaging clinically is usually reported as positive or negative, and the role of amyloid topography has not been studied before. To evaluate in a clinical setting the regional distribution patterns of C-Pittsburgh compound B (C-PIB) and the fluorine-18-fluorodeoxyglucose (F-FDG) uptake in patients with mild cognitive impairment (MCI), we designed this study. We studied 81 consecutive MCI patients, 64 amnestic (A-MCI) and 17 nonamnestic (NA-MCI) by C-PIB and F-FDG PET/computed tomography, by visual analysis. PIB retention was classified according to the regional distribution into the following patterns: A (frontal, lateral temporal, basal ganglia and anterior cingulate) and B (global retention). F-FDG images were considered positive only if temporoparietal hypometabolism consistent with Alzheimer's disease was observed. In 42 of the 64 A-MCI, C-PIB was positive. Twelve of the 42 positive A-MCI showed an A-pattern, all F-FDG negative, and 30 a B-pattern, 10 F-FDG positive and 20 F-FDG negative. Of the 17 NA-MCI, C-PIB was positive in three and F-FDG was positive in one. The different proportion of C-PIB positivity in A-MCI and NA-MCI was highly significant (P<0.001). Two different C-PIB patterns were observed in MCI patients and for the A-pattern, glucose hypometabolism consistent with Alzheimer's disease is highly unlikely. These findings may contribute towards a better selection of patients for future potential treatments and also to optimize the use of F-FDG-PET/CT.