Objective To perform a morphometric analysis of the upper cervical spine (UCS) by means of cone-beam computed tomography (CBCT) for the diagnosis of malformations or craniocervical instabilities in patients with cleft lip and palate (CLP) and class III malocclusion. Materials and Methods A total of 72 CBCTs from adult patients (48 male and 24 female) with Angle Class III malocclusion were divided into three groups: 1) Unilateral cleft lip and palate (UCLP) (n = 29; male = 65.5%; age = 24, 2 ± 4.2 years); 2) Bilateral cleft lip and palate (BCLP) (n = 18; male = 83.3%; age = 26.4 ± 6.0 years); 3) Control group (CON) (n = 25; male = 56.0%; age = 27.8 ± 9.3 years). The version 11.7 of the Dolphin® software (Chatsworth, California, USA) was used to evaluate the morphometric measurements and anomalies of the UCS. Data were analyzed by descriptive and inferential statistics (p ≤ 0.05). Results For the UCLP, BCLP and CON groups, respectively, the measures were: atlantodental interval (2.1 ± 0.5; 2.1 ± 0.4; 2.0 ± 0.3 mm), basion-opisthion (35.9 ± 3.2; 36.4 ± 3.0; 34.7 ± 1.9 mm), hyoid-C3 (34.5 ± 3.7; 34.5 ± 5.2; 35.3 ± 4.5 mm), and hyoid-sella (108.1 ± 9.8; 111.3 ± 9.2; 109.7 ± 10 mm); clivus-canal angle (152.3 ± 13; 150.3 ± 10; 150.7 ± 10°) and Torg-Pavlov index (1.0 ± 0.2; 1.0 ± 0.1; 1.1 ± 0.2). Potentially unstable anomalies and malformations were more prevalent in the UCLP group (34,4%). Conclusion Subjects with UCLP presented compressive or unstable anomalies on upper cervical spine, more frequently than controls and BCLP, despite the lack of statistically significant differences among groups. Future studies could increase the safety of patients and healthcare professionals specialized in craniofacial anomalies.