We assessed the accuracy of voxel-based morphometry (VBM) using a three-dimensional T1-weighted MRI in discriminating Alzheimer's disease (AD) in the very early stage of amnestic type of mild cognitive impairment and age-matched healthy controls. We randomly divided these subjects into two groups. The first group comprising 30 AD patients and 41 controls was used to identify the area with the most significant gray matter loss in patients compared to normal controls based on the voxel-based analysis of a group comparison. The second group comprising 31 patients and 41 controls was used to determine the discrimination accuracy of VBM. A Z-score map for a gray matter image of a subject was obtained by comparison with mean and standard deviation gray matter images of the controls for each voxel after anatomical standardization and voxel normalization to global mean using the following equation; Z-score=([control mean]-[individual value])/(control S.D.). Receiver operating characteristic curves for a Z-score in the bilateral medial temporal areas including the entorhinal cortex with the most significant loss in the first group showed a high discrimination accuracy of 87.8%. This result would open up a possibility for early diagnosis of AD using VBM.