Abstract
BACKGROUND: Ewing sarcoma (ES) is a rare malignancy primarily affecting children and adolescents, with cranial involvement representing less than 1% of cases. The sphenoid bone is an exceptionally uncommon site, presenting diagnostic and therapeutic challenges due to its proximity to neurovascular structures. OBSERVATIONS: We present the case of a 19-year-old male diagnosed at the age of 13 with ES in the sphenoid bone, extending into the anterior cranial fossa and orbit. The patient initially received chemotherapy and radiotherapy, resulting in partial regression; however, the patient experienced disease progression and underwent resection. Postoperative recovery was complicated by osteomyelitis, which was resolved with antibiotics and wound debridement. One year postoperatively, the patient was neurologically intact with stable imaging findings. A systematic review of the literature was conducted to identify similar cases of sphenoid ES and highlight their outcomes. LESSONS: ES of the sphenoid bone is a rare pathology that demands a high index of suspicion and a multidisciplinary treatment approach. Despite anatomical challenges, outcomes can be optimized through an aggressive multimodal therapy approach. Continued research is needed to establish standardized treatment protocols and improve long-term survival. https://thejns.org/doi/10.3171/CASE25427.