To investigate the association between maxillofacial morphology and mandibular bone volume in patients with skeletal malocclusion. Subjects were 118 adult Japanese (58 males and 60 females). Skeletal malocclusion was classified, based on cephalometric analysis, into skeletal Classes I (-1° ≤ ANB < 4°), II (ANB ≥ 4°), and III (ANB < -1°). Using cone-beam computed tomography and three-dimensional image analysis software, the dental crowns and mandible were separated, with only the mandible extracted. This was then reconstructed as a three-dimensional model, from which the mandibular volume was measured. No significant difference in mandibular volume was noted among skeletal Classes I, II, and III, nor was there any significant correlation between mandibular volume and the ANB, SNB, or mandibular plane angles. There was occasional and limited correlation between mandible volume and gonial angle and certain cephalometric distance parameters. We conclude that proper understanding of the three-dimensional maxillofacial morphology requires not only cephalometric radiographic tracings but also high-resolution analysis of the mandibular area, width, and volume.