OBJECTIVE: To investigate morphologic changes in the somatosensory cortex and the thickness of the corpus callosum subdivisions that provide interhemispheric connections between the 2 somatosensory cortical areas. METHODS: Twenty-eight patients with severe restless legs syndrome (RLS) symptoms and 51 age-matched healthy controls were examined with high-resolution MRI at 3.0 tesla. The vertex-wise analysis in conjunction with a novel cortical surface classification method was performed to assess the cortical thickness across the whole-brain structures. In addition, the thickness of the midbody of the corpus callosum that links postcentral gyri in the 2 hemispheres was measured. RESULTS: We demonstrated that a morphologic change occurred in the brain somatosensory system in patients with RLS compared to controls. Patients with RLS exhibited a 7.5% decrease in average cortical thickness in the bilateral postcentral gyrus (p < 0.0001). Accordingly, there was a substantial decrease in the corpus callosum posterior midbody (p < 0.008) wherein the callosal fibers are connected to the postcentral gyrus, suggesting altered white matter properties in the somatosensory pathway. CONCLUSION: Our results provide in vivo evidence of morphologic changes in the primary somatosensory system, which could be responsible for the sensory functional symptoms of RLS. These results provide a better understanding of the pathophysiology underlying the RLS sensory symptoms and could lead to a potential imaging marker for RLS.