We used diffusion tensor imaging to assess callosal morphology in 35 pairs of monozygotic twins, of which 17 pairs were concordant for handedness and 18 pairs were discordant for handedness. Functional hemispheric language dominance was established for each twin member using fMRI, resulting in 26 twin pairs concordant and 9 twin pairs discordant for language dominance. On the basis of genetic models of handedness and language dominance, which assume one “right shift” (RS) gene with two alleles, an RS+ allele biasing toward right-handedness and left cerebral language dominance and an RS− allele leaving both asymmetries to chance, all twins were classified according to their putative genotypes, and the possible effects of the gene on callosal morphology was assessed. Whereas callosal size was under a high genetic control that was independent of handedness and language dominance, twin pairs with a high probability of carrying the putative RS+ allele showed a connectivity pattern characterized by a genetically controlled, low anisotropic diffusion over the whole corpus callosum. In contrast, the high connectivity pattern exhibited by twin pairs more likely to lack the RS+ allele was under significantly less genetic influence. The data suggest that handedness and hemispheric dominance for speech production might be at least partly dependent on genetically controlled processes of axonal pruning in the corpus callosum.