Albers-Schönberg disease is a rare bone syndrome characterized by increased bone density and infectious complications after dental extraction or minor surgery. The prosthodontic management of such edentulous patients with osteomyelitis is very challenging and requires special strategies due to a high risk of failure and worsening of the condition. This clinical report describes the rehabilitation of a 31-year-old edentulous woman presenting with Albers-Schönberg disease, secondary chronic osteomyelitis, maxillary hypoplasia, compromised oral conditions, temporomandibular disorders, and psychologic distress. The treatment included a mandibulectomy and removable prostheses. A crucial element for the successful long-term treatment and quality of life improvement observed in this patient was the 1-year transitional phase with interim dentures and frequent follow-up appointments. The complications and management proposed during a 10-year follow-up are presented. Int J Prosthodont 2023;36:642–648.