OBJECTIVES: To estimate the budget impact in Belgium of denosumab (120 mg) in the treatment of GCTB, an extremely rare, locally aggressive benign tumor often leading to severe destruction of bone and extension into the surrounding soft tissues. METHODS: A budget impact model was developed, combining epidemiological data, proportions of resectable and unresectable GCTB disease, and eligibility for treatment with denosumab. Evidence collected in clinical trials is used to estimate the denosumab clinical effect. Publicly available costs of the relevant surgical procedures and the actual cost for denosumab 120 mg from payer perspective are considered. The clinical effect of denosumab in delaying or downgrading invasive surgeries is estimated by comparing the surgical procedures planned at trial entry and the procedures actually performed during the trial. To calculate the savings in surgical procedures, the downgrade in planned procedures and only 50% of the avoided procedures in the trial period were considered. Resource use associated with the surgical procedures included the need for rehabilitation and re-hospitalizations due to complications. Savings were only applied to patients with resectable tumors. The model does not take into account the full clinical benefit of denosumab including decrease in disease progression in patients who have not undergone surgery. The time horizon considered was 3 years.  RESULTS: Denosumab is expected to be provided to 32, 42 and 53 patients in year 1, 2 and 3, respectively. 550,940 euros of total drug expenditure are expected. Savings were estimated at 409,372 euros, the majority of which was attributable to fewer and less severesurgical procedures. The impact of denosumab on the overall health care budget is 141,568 euros over three years.  CONCLUSIONS: The introduction of denosumab in the treatment of GCTB has a manageable budget impact in Belgium. Seventy four percent of the denosumab expenditure is off-set thanks to its clinical benefit.