It has yet to be established whether neurological soft signs (NSS), which include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing of complex motor tasks, result from specific or diffuse brain structural abnormalities. Studying the neuroanatomical basis of NSS in healthy individuals may help to identify which brain areas are specifically associated with these signs, while excluding the potential confounding effects of psychiatric and neurological disorders. We investigated the relationship between brain structure and NSS in 43 healthy individuals, using the Neurological Evaluation Scale for neurological assessment, and high resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of NSS were associated with a reduction of inferior frontal gyrus, middle and superior temporal gyrus, and anterior cingulate gyrus. It is of note that in a previous study of patients with psychosis we found that an excess of NSS was associated with a reduction of similar cortical areas. Therefore, we suggest that these cortical brain structural changes represent a common neuroanatomical substrate of NSS, across healthy individuals and patients with psychosis.