Benign fibro-osseous lesions are a group of pathological conditions characterized by the replacement of normal bone with cellular fibrous connective tissue that undergoes mineralization. The most common types of benign fibro-osseous lesions include fibrous dysplasia, ossifying fibroma, and osseous dysplasia. However, diagnosing these lesions can be challenging due to their overlapping clinical, radiological, and histological features, which can cause a diagnostic dilemma for surgeons, radiologists, and pathologists. One rare type of benign fibro-osseous lesion is the cemento-ossifying fibroma (COF), which is a definitive form of a benign fibro-osseous tumor that affects the craniofacial region, particularly the jaws (70%). Here, we present a case of COF in a 61-year-old female patient in the maxillary anterior region. Due to a clear distinction between the lesion and healthy bone, the lesion was treated with conservative surgical excision followed by curettage and primary closure. However, differential diagnosis of COF can be highly challenging for clinicians due to its overlapping features with other fibro-osseous lesions like Paget’s disease and fibrous dysplasia. Ossifying fibroma and fibrous dysplasia often present a histopathological, clinical, and radiological overlap. The post-operative follow-up after eight months was unpredictable, with a radiological picture showing the increased thickness of the frontal bone, parietal bone, and maxilla with obliteration of marrow spaces, alteration of the trabecular pattern with a cotton wool/ground glass appearance, and reduced maxillary sinus space. Proper evaluation and diagnosis of fibro-osseous lesions are necessary before arriving at a final conclusion. Cemento-ossifying fibroma in the maxillofacial skeleton is uncommon, and after eight months, the recurrence rate is rare. This case highlights the importance of considering COF as a differential diagnosis for fibro-osseous lesions in the maxillofacial region and the necessity for proper evaluation and diagnosis to determine the appropriate treatment plan and prognosis. In summary, the diagnosis of benign fibro-osseous lesions can be challenging due to their overlapping features, but early diagnosis and proper evaluation are essential for successful treatment outcomes. COF is a rare type of benign fibro-osseous lesion where other fibro-osseous lesions in the maxillofacial region should be considered as a differential diagnosis, and the necessary steps should be taken to confirm the diagnosis before arriving at a final conclusion.