Importance: Delayed clinical and molecular diagnoses of craniofacial malformations are common due to limited awareness and understanding of these conditions, leading to significant gaps in management and treatment. Objective: To describe the clinical characteristics of patients with craniofacial malformation, identify the most frequent genomic loci associated with these disorders in our population, and evaluate the time interval between clinical and molecular diagnoses. Design and Setting: This retrospective chart review included patients enrolled in the Estudio Colaborativo Latinoamericano para Malformaciones Congenitas (ECLAMC) cohort at the Fundacion Valle del Lili from 2011 to 2022. Participants: Patients were identified using ICD-11 codes for congenital malformations of the eye, ear, face, neck, cleft lip, and cleft palate. All patients with documented craniofacial malformation were included. Main Outcomes and Measures: The study assessed novel variants and genes associated with craniofacial malformations, characterized the phenotypic spectrum, and determined delays in molecular diagnosis. Results: A total of 145 patients were included; the median age was 13 years (IQR 6.6 to 18.7), and 85 (58.6%) were male. Syndromic phenotypes were identified in 42 of 145 patients, 72 of 145 had isolated craniofacial abnormalities, and 30 of 145 lacked a definitive phenotypic diagnosis. Common malformations included eyelid anomalies, cleft lip, macrocephaly, microcephaly, craniosynostosis, and microtia. Only 23 patients (15.8%) had a confirmed molecular diagnosis. Identified syndromes included Cowden, Pfeiffer, CHARGE, Meckel-Gruber, and Joubert syndromes. Pathogenic variants were observed in genes such as GLI3, CHD7, FGFR2, HEXA, YARS2, ACVR1, AHDC1, TYR, RAD50, BRCA2, ANKS6, TP63, SOX9, COCH, KATNIP, CREBBP, SHH, MITF, FGFR3, EFTUD2, RPS6KA3, RERE, PTEN, OTC, L1CAM, RELN, ETHE1, HS6ST2, EFNB1, AMER1, and PTPN11. VUS were detected in TP63, STAMBP, OCLN, and FRMPD4. In 13% of cases, molecular diagnosis was not established. Conclusions and Relevance: Clinical and molecular characterization distinguishes syndromic from non-syndromic craniofacial malformations and informs comprehensive care. Significant diagnostic delays highlight the need for early genetic testing to guide treatment and provide timely counseling for patients and their families.