The anatomical factors underlying reorganization of language representation are yet to be elucidated, although correlations between asymmetric structures and language lateralization have been identified. Previous research has implicated the corpus callosum in the development of language lateralization. This study examined the relationship between callosal morphology and language asymmetry, using letter fluency functional magnetic resonance imaging, in 13 patients with focal epilepsy and 8 healthy controls. Regional callosal thickness was determined without relying on a priori delineation of callosal segments. We predicted that language asymmetry measured by fMRI activation laterality scores would be correlated with regional callosal thickness in both groups. However, only the degree of language activation asymmetry was significantly correlated with callosal thickness in the isthmus and the midbody of patients, and there was a significant interaction between the groups with respect to callosal thickness and language activation asymmetry. These data suggest that callosal pathways may be important for language reorganization in the context of early cerebral injury.