Objective: To present pathologic, clinical, and treatment findings for giant cell tumors (GCTs) of sphenoid bone and clivus. Methods: We describe the optimal treatment algorithm in patients with a histopathologic diagnosis of bone GCT by presenting the effects of denosumab treatment in both pediatric and adult patients with GCT undergoing endoscopic transnasal surgery. Clinicopathologic correlation is crucial for the differential diagnosis of GCT and the choice of treatment modality. Conclusion: GCT of bone is a local aggressive tumor that accounts for about 3%-7% of all bone tumors. GCTs located in the cranium are extremely uncommon neoplasms. There are no defined guidelines for the treatment of GCTs in skull base. Following surgical resection of the tumor, the addition of denosumab treatments to radiotherapy has a significant role in preventing the recurrence of GCT and in promoting regression of residual tumor size.