This article demonstrates a methodological approach to diagnosing a periapical radiolucency that could not be diagnosed using only basic clinical and radiographic findings. The patient was a 59-year-old Hispanic female with a small tender mass on the lower gingiva associated with tooth #25. Radiographic appearance demonstrated a well-defined radiolucent lesion at the apices of the mandibular incisors. The patient had no significant medical history. Cone-beam computed tomography (CBCT) showed bony expansion of the buccal plate. Differential diagnosis included non-endodontic unilocular radiolucent lesions in the anterior mandibular region. Biopsy findings were consistent with periapical cemento-osseous dysplasia (PCOD). In conclusion, clinical appearance of PCOD varies from non-expansile and asymptomatic to being expansile and sometimes symptomatic. In the latter cases, it may be necessary to use additional diagnostic tools to confirm the diagnosis.