The association between cranial-base morphology and Class III malocclusion is not fully understood. The purpose of this study was to investigate the morphologic characteristics of the cranial base in children with Class III malocclusion. Lateral cephalograms from 100 children with Class III malocclusion were compared with those from 100 subjects with normal occlusion. Ten landmarks on the cranial base were identified and digitized. Cephalometric assessment using seven angular and 18 linear measurements was performed by univariate and multivariate analyses. The results revealed that the greatest between-group differences occurred in the posterior cranial-base region. It was concluded that shortening and angular bending of the cranial base, and a diminished angle between the cranial base and mandibular ramus, may lead to Class III malocclusion associated with Class III facial morphology. The association between cranial-base morphology and other types of malocclusion needs clarification. Further study of regional changes in the cranial base, with geometric morphometric analysis, is warranted.