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Objective: MRI-based measurements of hippocampal atrophy are a sensitive indicator of the early pathologic degeneration of the medial temporal lobe in AD. However, AD pathology appears first in the transentorhinal/entorhinal cortex, not the hippocampus. The authors tested the hypothesis that MRI-based measurements of the entorhinal cortex are more sensitive than measurements of hippocampal volume in discriminating among three clinical groups; controls, patients with a mild cognitive impairment (MCI), and patients with mild probable AD. Methods: The authors studied 30 controls, 30 patients with MCI, and 30 patients with AD who were matched among clinical groups on age, gender, and education. All underwent a standardized MRI protocol from which the authors made measurements of hippocampal volume, entorhinal cortex volume, and the cumulative length of the medial border of the entorhinal cortex. Results: Pairwise intergroup differences ( p Conclusions: Despite the theoretical rationale for the superiority of entorhinal measurements in early AD, the authors found MRI measurements of the hippocampus and entorhinal cortex were approximately equivalent at intergroup discrimination. Measurements of the hippocampus may be preferable because MRI depiction of the boundaries of the entorhinal cortex can be obscured by anatomic ambiguity, image artifact, or both.