Glandular odontogenic cyst (GOC) is a rare developmental cyst, comprising <0.5% of odontogenic cysts. Its overlap with other lesions, particularly dentigerous cysts (DCs), makes diagnosis challenging. This study aimed to compare the clinicopathologic characteristics of GOCs and DCs to aid in differential diagnosis and treatment planning.

Patient records with GOC and DC from 1996 to 2025 were reviewed. Demographic, clinical, and radiographic data were collected, and histopathological slides were re-evaluated to assess eight epithelial features. GOC spectrum (GOCS) lesions were classified as classic GOC (≥5 features) or GOC-like (3–4 features). Categorical variables were analyzed using SPSS software with exact statistical procedures (Fisher’s exact test and the Fisher–Freeman–Halton exact test; p < 0.05), with Holm correction applied for multiple histopathological comparisons.

A total of 43 GOCS (39 classic GOCs and 4 GOC-like) and 34 DCs were evaluated. Classic GOCs peaked in the 5th decade, whereas DCs occurred predominantly in the 4th decade. However, GOC-like lesions presented at an older mean age of 52.2 years, with no predominant decade. GOCs were associated with the anterior jaw regions, whereas DCs predominantly involved the posterior mandible. A unilocular pattern predominated across all groups, whereas radiographic association with an impacted or unerupted tooth was significantly more frequent in DCs. Excisional biopsy (enucleation) specimens predominated across all three groups. Histopathological feature frequencies differed between GOCs and DCs. Exploratory comparisons of classic GOCs and GOC-like lesions yielded nominal differences for certain epithelial features, but these findings were based on a small denominator, resulting in limited clinical interpretability.

Accurate diagnosis requires integrating demographic, clinical, radiographic, and histopathological findings. Furthermore, differentiation between GOCs and DCs may be guided by various clinical and paraclinical factors. However, identifying GOC-like lesions can be challenging, as incomplete expression of characteristic histopathological features, particularly in incisional biopsy specimens, does not exclude GOC. Given the small number of GOC-like lesions, conclusions related to this subgroup should be interpreted cautiously and regarded as descriptive rather than confirmatory.