Objective: To investigate whether global and regional β-amyloid (Aβ) burden as measured with C Pittsburgh compound B (PIB) PET is associated with hippocampal atrophy characterized using MRI in healthy controls and patients with amnestic mild cognitive impairment (aMCI) or Alzheimer disease (AD). METHODS: Ninety-two elderly healthy controls, 32 subjects with aMCI, and 35 patients with AD were imaged using C-PIB PET and MRI. Hippocampal volume was measured and PIB standardized uptake value ratio was extracted after partial volume correction within 41 regions of interest. Global, regional, and voxel-based correlations between PIB and hippocampal volume were computed for each group. RESULTS: In healthy control participants with elevated neocortex PIB retention, significant correlation was found between PIB retention in the inferior temporal region and hippocampal volume using both region-based and voxel-based approaches. No correlation was found in any other group. CONCLUSIONS: The strong correlation between hippocampal atrophy and β-amyloid (Aβ) burden in the Pittsburgh compound B-positive healthy control group suggests that Aβ deposition in the inferior temporal neocortex is related to hippocampal synaptic and neuronal degeneration.