Objective: The purpose of this investigation was to study the development of the premolars in a sample of Greek children with cleft lip and palate. Method and materials: The study material consisted of panoramic radiographs of 34 individuals (22 boys and 12 girls) with cleft lip with or without cleft palate. The boys ranged from 9.0 to 14.0 years of age and the girls ranged from 8.0 to 14.5 years of age. The mean age was 11.3 years. Each panoramic radiograph was matched with a corresponding one of an unaffected individual of the same sex and chronologic age (± 3 months). The panoramic radiographs were used to categorize the stages of tooth development according to the 10 stages of mineralization described by Nolla. The assessment was repeated by a second observer. Results: Individuals with clefts exhibited a statistically significant delay of formation and mineralization of the maxillary right and left second premolars and the mandibular right second premolar in comparison to individuals without clefts. In the cleft group, there was no statistically significant difference between boys and girls in premolar development. No asymmetric development of contralateral premolar teeth was observed in individuals with cleft lip and palate. Conclusion: Although the exact biologic explanation remains to be found, the formation of premolars is delayed in children with cleft lip and palate.