A fibro-osseous lesion is a condition where the regular bone is changed with a fibrous connective tissue matrix that includes an abnormal bone or cementum. These lesions are divided into three groups: ossifying fibroma, cemento-osseous dysplasia (COD), and fibrous dysplasia. COD is the most recurring benign fibro-osseous lesion. These lesions are usually not detected unless infected and are commonly noted accidentally on an X-ray. In this report, we demonstrate a case of periapical cemento-osseous dysplasia in a medically compromised patient with multiple systemic diseases.