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Introduction The RANK ligand inhibitor denosumab has been used to treat cases of unresectable giant cell tumors of bone (GCTB) or preoperatively to facilitate intralesional curettage. However, there are no clear guidelines for use of denosumab prior to en bloc resection. Case Presentation In this study, a 26-year-old patient presented with atraumatic lateral knee pain. X-rays demonstrated a destructive lesion within the proximal fibula, and biopsy confirmed the diagnosis of GCTB. Management and Outcomes The patient received 3 months of neoadjuvant denosumab with complete resolution of his pain and cortical rim formation surrounding the tumor. The tumor was removed en bloc with negative margins. At 6-month follow-up, the patient had returned to his functional baseline with no evidence of tumor recurrence. Conclusion Neoadjuvant denosumab can mitigate symptoms related to GCTB and promotes cortical bone formation, facilitating en bloc resection and permitting acceptable functional outcomes in select cases. [ABSTRACT FROM AUTHOR]