Consistency of right-hand preference correlates with callosal isthmus size. Anterior corpus callosum (CC) regions vary as a function of sex and right- versus left-hand preference. We analyzed regional CC anatomy in a sample of right- and left-handed men and women on the basis of both degree (“Consistency”) and direction (“Hand”) of hand preference scores. Significant Hand × Consistency effects indicated that both are important factors in CC organization. These data also suggested that a single continuum of hand preference and regional CC size may not be applicable across all subjects.