The purpose of this retrospective longitudinal cephalometric study was to investigate differences in craniofacial and especially mandibular morphology between patients with Pierre Robin sequence and isolated cleft palates. The experimental group comprised 96 patients (54 males and 42 females) with a history of Pierre Robin sequence. This group was compared cephalometrically with a control group of 50 patients (25 males and 25 females) with a history of isolated clefting of the palate. All 96 patients in the PR group had a lateral cephalogram at a mean age of 5.5 years. Thirty-eight of those patients had additional cephalograms at the mean ages of 10.3 years and 16.8 years. All patients in the cleft palate group had 3 corresponding cephalograms at the following mean ages: 5.7 years, 10.6 years, and 17.0 years. Twenty-nine cephalometric measurements were performed on each cephalogram with the use of computerized cephalometric software. Significant differences were identified between the 2 groups, particularly in the size and sagittal position of the mandible, which was consistently shorter in the Pierre Robin group at all 3 ages. Less severe differences were noted in the inclination of the palatal plane, the facial height proportions, and the midface depth. We conclude that patients with Pierre Robin sequence have a significantly smaller mandible as compared with patients with isolated cleft palate, and the difference does not change after the age of 5 years.