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Non-endodontic lesions (NEL) closely resemble lesions of endodontic origin. Its etiology can be odontogenic, non-odontogenic, neoplastic, or anatomic variations that can resemble inflammatory periapical lesions in the periapical area. Inflammatory periapical lesions are caused by pulpal pathoses and require endodontic treatment. Since numerous NEL may resemble inflammatory periapical lesions, they can lead to misdiagnosis and inappropriate management. Thus, a detailed review of the patients’ medical and dental histories with clinical examination, including radiographic findings, is essential for the proper assessment of periapical lesions. Numerous cases of misdiagnoses of NEL have been reported in literature. Thus, this review aimed to strengthen the awareness of clinicians on periapical radiolucency, which may resemble inflammatory periapical lesions.