The association between craniofacial morphology and congenitally missing teeth is at present unclear. The aims of this study were to investigate whether hypodontia is associated with changes in the sagittal skeletal profile and to identify putative relationships between the skeletal profile and the severity of hypodontia. In a cross-sectional analytical study, the craniofacial structure and profile based on two-dimensional lateral cephalograms of Southern Chinese hypodontia patients (n = 49, 24 males, 25 females, mean age 16.4 years) and a comparison group without hypodontia (n = 41, 15 males, 26 females, mean age 16.7 years) were compared. The hypodontia patients were divided into three subgroups according to the severity of hypodontia (mild: or =10 congenitally missing permanent teeth). All hypodontia patients had a significantly reduced mandibular plane, ANB, and face height compared with the control group (P < 0.05). A significant increase in chin thickness was also observed in the hypodontia patients (P < 0.05). As the severity of hypodontia increased from moderate to severe, a tendency to develop a retrognathic maxilla and a Class III skeletal relationship was noted in addition to the above features, making the already thick chin even more prominent. Statistically significant correlations (Pearson's correlation coefficient) were found between the number of missing teeth and SNA, NAFH, and ANB angles, the mandibular plane, chin thickness, and face height. In Southern Chinese subjects, hypodontia was associated with a shorter face, a flatter mandibular plane, a more pronounced chin, and a Class III skeletal profile. In severe hypodontia subjects, the maxilla was more retrognathic with a greater predilection to a Class III skeletal relationship.