BACKGROUND: This cross-sectional observational study seeks to determine the clinical differences in eruption failure of permanent first molars presenting in cases of ankylosis, failure due to mechanical obstruction (MFE), and failure due to genetic causes (PFE). A total of 34 patients between 7 and 12 years old (mean ± SD: 9.3 ± 1.28 years), with anomalies in the eruption of the first permanent molars, were selected based on clinical observation, the evaluation of orthopanoramic radiographs, and intra- and extra-oral photographs. Genetic testing was also conducted to identify variants of the PTH1R gene in 27 patients with clinical signs of PFE. The familial nature of the condition was investigated through anamnesis of the first-degree relatives. RESULTS: Out of the 34 patients, 3 were diagnosed with PFE, confirmed by the presence of PTH1R variants. Twelve patients showed clinical signs suggestive of MFE diagnosis. The remaining 19 cases, in which no variants of the PTH1R gene were found, were considered cases of ankylosis. Roots in ankylosed teeth were located in the basal bone and often dilacerated. The reduction of vertical growth of the alveolar bone was present in both PFE and ankylosis cases, but teeth were nearer to the basal bone in ankylosis cases. Infraocclusion of deciduous teeth was present in PFE and MFE cases. Asymmetry due to bilaterally unbalanced eruption of the teeth was present in six cases with ankylosis. Bilateral affection was noticed in one PFE case and 6 MFE cases. A descriptive statistical analysis using Fisher's exact test was employed to evaluate the significant association between variables. CONCLUSIONS: The study highlighted some characteristic signs that help in early diagnosis of cases of PFE, MFE, and ankylosis. However, genetic testing remains necessary to understand the nature of the most dubious cases.