Chronic non-suppurative osteomyelitis (CNSO) is a chronic bone disease and may be associated with a reparative periosteum entity called proliferative periostitis (PP). This condition rarely affects the maxillofacial region. Mandibular cases were already described for an infectious dental cause, often with an "onion skin" radiographic aspect, but some rare reported cases showed no obvious etiology. They represent a challenge for diagnosis because of possible misdiagnosis leading to unsuccessful or inappropriate treatment attempts. An uncommon case of mandibular CNSO associated with PP in a 9-year-old boy with no obvious infectious or inflammatory causes is reported. Clinical and radiographic examinations revealed a swelling in the left hemimandible, associated with multiple osteolytic areas inside both medullary and newly formed periosteal bone and cortical bone perforations. Recovery signs were seen after a 22-month follow-up period, and radiographic signs of bone healing were observed. From this new case report, a review of the literature was performed on reported cases of mandibular CNSO with PP, and discussed the etiological, clinical, radiologic, and therapeutic aspects of this pathology. This work highlights the importance of considering CNSO with PP in the differential diagnosis of one-sided painless mandibular swellings, even in the absence of an obvious cause.