A dentigerous cyst (DC) is the most common developmental cystic lesion of the jaws. Histologically, these cysts derive from the odontogenic epithelium that includes the reduced enamel epithelium, epithelial cell rests of Serres, and epithelial cell rests of Malassez. Radiographically, DCs are usually presented as well-defined radiolucencies associated with the crown of an unerupted tooth at the level of the cementoenamel junction (CEJ). Glandular odontogenic cysts (GOCs) are classified under the same category as DCs. Radiographically, glandular odontogenic cysts (GOCs) may appear as unilocular or more commonly as multilocular radiolucencies with well-defined margins. It is evident that there is a significant overlap in the radiographic features of the two pathologies. This case report describes one of those cases. A 49-year-old male patient was referred for a cone beam computed tomography (CBCT) imaging series for the evaluation of possible pathology in areas #17-#19 and ramus to the Graduate Oral and Maxillofacial Radiology Clinic, Health Science Center, San Antonio, University of Texas. The radiographic interpretation revealed a well-defined corticated low-density lesion in the left mandibular molar-ramus region. The mandibular canal was intact and traceable but displaced buccally and inferiorly. The radiographic findings were suggestive of a slow-growing odontogenic process, most likely cystic. Marsupialization and incisional biopsy of the lesion were carried out, which was highly suggestive of GOC. Two months after the initial incisional biopsy, it was decided that enucleation and curettage, as well as extraction of #17, #18, and #19, should be carried out. The enucleated specimen was sent to the histopathology laboratory for evaluation. The second biopsy showed a dentigerous cyst associated with impacted #17. Histopathology continues to be, statistically, the most reliable method for diagnosing these types of abnormalities. However, in certain cases, such as this one, the accuracy of histopathological examination may falter due to overlapping characteristics and different histopathological features based on the location of acquisition of the specimen. The initial radiographic estimation included the differential diagnosis of a DC as a second differential and, although contradicted by the first biopsy result, was eventually supported by the second final biopsy of the entire specimen. Although DCs do not tend to recur, the need for regular follow-ups should not be underestimated, neither by the attending clinician nor by the patients themselves. In conclusion, the radiographically proven, uneventful wound healing constitutes the only reassurance for the patient's well-being., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zisis et al.)