The effectiveness of maxillary expansion and face-mask therapy in children with Class III malocclusion was studied in a sample of 46 subjects in mixed dentition and compared with a control sample of 32 subjects with untreated Class III malocclusion. Treated and untreated samples were divided into early and late mixed-dentition groups to aid identification of the optimum timing of the orthopedic treatment of the underlying skeletal disharmony. Cephalometric analysis was based on a stable basicranial reference system, appropriate for longitudinal studies started in the early developmental ages. The level of significance for intergroup comparisons was set at a p value of 0.01. Significant forward displacement of the maxillary complex was found in the early-treatment group. The region of the pterygomaxillary suture, in particular, showed significant changes in the subjects treated during early mixed dentition. No significant maxillary modifications were recorded in the late-treatment group. Both early and late groups exhibited smaller increments in mandibular protrusion and larger increments in the intermaxillary vertical relationship compared with their respective Class III control groups. Only children treated at an early age, however, showed a significant upward and forward direction of condylar growth, leading to smaller increments in total mandibular length. These results indicate that the combination of a bonded maxillary expander and face-mask therapy is more effective in early mixed dentition than in late mixed dentition, especially with regard to the magnitude of the protraction effects on maxillary structures.