Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease with erythrocyte membrane dysfunction, progressive hyperkinesia, and neuropsychological abnormalities. Neuropathologic and neuroimaging investigations demonstrate damage to the basal ganglia. Here, a novel automated technique of voxel-based magnetic resonance imaging (MRI) analysis was applied to determine the volumes of caudate nucleus and putamen in nine patients with proven ChAc in comparison with 257 healthy controls. At individual subject level, ChAc patients and controls could be reliably discriminated by the volume of the caudate, using a cut-off of 5 ml, or by a value of -3 in terms of z scores. Putaminal volumes were also significantly reduced in ChAc patients, but showed some overlap with controls. The results indicate that this new automated volumetric MRI analysis offers an objective imaging tool for identification of ChAc patients by quantification of basal ganglia atrophy and lends itself to extension to other basal ganglia diseases.