IntroductionRadiolucent lesions with gingival swelling found in the premolar and intercanine region can elicit a different clinical diagnosis than one confirmed by histologic findings. The purpose of the study is to identify and present the frequency of the unexpected microscopic diagnosis of odontogenic keratocyst (OKC) in a location preoperatively favoring a lateral periodontal cyst (LPC) with similar clinical and radiographic appearance. MethodsA retrospective analysis of biopsies received from 2011 and 2019 was performed, and the number of LPC and OKC cases was assessed. The alignment of clinical and radiographic diagnosis to histologic findings and anatomic location was analyzed, and the number of OKC cases preoperatively misdiagnosed as LPCs was identified. ResultsA total of 79,257 biopsies were received. Of those, 184 were diagnosed as LPCs and 742 as OKCs. For all preoperatively diagnosed LPCs, the clinical and histologic diagnosis aligned; however, 182 of 742 OKCs were submitted with a clinical misdiagnosis of LPCs. The location of these lesions with the unanticipated diagnosis overlapped with those for LPCs, specifically the maxillary and mandibular anterior and premolar regions. ConclusionsRadiolucent lesions with gingival swelling in the premolar and intercanine region are frequently clinically and radiographically misdiagnosed. A biopsy should be considered in all cases to establish the correct pathologic diagnosis and treatment course.