Background Osteopathia striata with cranial sclerosis (OSCS) is a rare x-linked genetic disorder that has variable clinical findings but specific radiographic features, which include marked sclerosis of the long bones and axial skeleton, including the skull. Linear striations, commonly seen in the long bones, are the basis for the name osteopathia striata. Maxillofacial manifestations can include a cleft palate, high palatal vault, midface hyperplasia, hypoplastic maxillary sinuses, enlarged alveolar bone processes, temporomandibular joint (TMJ) abnormalities, and dense mandibular bone with variable striations. Dental abnormalities have been poorly documented but include delayed eruption of permanent teeth, missing teeth, short roots, and microdontia. Study Design A 44-year-old male was referred to the University of Florida College of Dentistry for evaluation and treatment of temporomandibular disorder (TMD). A pantomograph was exposed to assess TMJ dysfunction related to progressive bony overgrowth of craniomaxillofacial skeleton and ankylosis, which had previously been surgically treated. His medical history was significant for OSCS, cleft lip and palate, obstructive sleep apnea, bronchitis, asthma, disk herniation, arthritis, diabetes, and chronic kidney disease. The radiographic assessment was limited because of severe sclerosis of the cranium, displayed as multiple lobulated appearances and homogeneous radiopaque entities superimposed on the maxilla, TMJs, and the sphenoid, mastoid, and temporal bones. The visualized cortical outlines of the maxilla and the mandible appeared dense, thick, and sclerotic. Discussion/Conclusions OSCS is a rare disorder. Diagnosis can often be challenging because other diseases, such as osteopetrosis, pyknodysostosis, Paget disease of bone, and other sclerosing bone dysplasias, make this difficult to diagnose. Radiologists should be aware of the specific radiographic appearance of this condition to aid in the proper diagnosis and management of these patients.