We have examined gender differences of cortical thickness using a 3-D surface-based method that enables more accurate measurement in deep sulci and localized regional mapping compared to volumetric analyses. Cortical thickness was measured using a direct method for calculating the distance between corresponding vertices from inner and outer cortical surfaces. We normalized cortical surfaces using 2-D surface registration and performed diffusion smoothing to reduce the variability of folding patterns and to increase the power of the statistical analysis. In stereotaxic space, significant localized cortical thickening in women was found extensively in frontal, parietal and occipital lobes, including the superior frontal gyrus (SFG), superior parietal gyrus (SPG), inferior frontal gyrus (IFG) and postcentral gyrus (PoCG) in the left hemisphere and mostly in the parietal lobe, including the SPG in the right hemisphere. In the temporal lobe, small regions of the left and right caudal superior temporal gyrus (STG) and the left temporal pole showed significantly greater cortical thickness in women. The temporal lobe shows relatively less significant thickening than other lobes in both hemispheres. In native space, significantly greater cortical thickness in women was detected in left parietal region, including SPG and PoCG. No significant local increases of cortical thickness were observed in men in both spaces. These findings suggest statistically significant cortical thickening in women in localized anatomical regions, which is consistent with several previous studies and may support a hypothesis of sexual dimorphism.