Severe hypercalcemia caused by primary hyperparathyroidism mandates prompt parathyroidectomy but increases intra-operative risk, and consequently serum calcium levels should be lowered before surgery. We report two patients with severe hypercalcemia and moderate renal impairment treated with the monoclonal antibody denosumab as a bridge to surgery, although the drug had never been used so far for this purpose. The antiresorptive drug denosumab interferes with the RANKL/RANK (Receptor Activator of Nuclear Factor κ B-ligand/Receptor Activator of Nuclear Factor κ B) signaling, thus inhibiting bone resorption, allowing the quick attainment of adequate serum calcium levels. Our cases suggest the possible use of denosumab in the pre-surgical management of severe hypercalcemia, resulting from both benign and malignant parathyroid disease. Such a “bridge” therapy could be suitable for allowing a prompt and safer parathyroidectomy even in patients with impaired renal function.