This paper aims to report a case in which central giant cell granuloma (CGCG) mimicked a periapical lesion of endodontic origin. An 18‐year‐old female patient was referred for diagnosis and treatment of extensive radiolucent periapical lesion involving 31, 32, 33, 34 and 35 teeth. Clinically, the patient presented slight facial asymmetry and healthy teeth on the affected side with positive response to thermal vitality tests. Thus, an incisional biopsy was performed, which presented a histopathological picture characteristic of a CGCG. The endodontic treatment of the involved teeth was followed by surgical curettage of the lesion. After two years of follow‐up, the patient was asymptomatic, with marked improvement in mandibular symmetry and adequate healing of the lesion. Therefore, the diagnosis of radiolucent periapical lesions must include lesions of endodontic and non‐endodontic origin for better treatment planning and execution.