Abstract Objectives Ectopic parathyroid hormone (PTH) secretion is rare in children with rhabdomyosarcoma, and only a few pediatric cases have been reported to date. Reports of the use of zoledronic acid (ZA) and Denosumab are limited for the treatment of hypercalcemia of malignancy (HCM) in the pediatric population. The aim of presenting this pediatric case of rhabdomyosarcoma accompanied by HCM, secondary to ectopic PTH secretion, was to highlight the benefits of ZA as a first-choice bisphosphonate in this situation with Denosumab as an alternative therapy. Case presentation The patient was diagnosed at 13 years with alveolar rhabdomyosarcoma. Multiple bone metastases first appeared at 15 years, but he remained normocalcemic until 17 years old when serum calcium was 15.1 mg/dL and PTH 249 pg/mL. While serum calcium responded well after ZA and Denosumab cycles, PTH remained elevated, reaching a peak value of 1851 pg/mL during treatment cycles. Conclusions We report a patient with rhabdomyosarcoma accompanied by HCM, secondary to ectopic PTH, in whom the HCM was successfully managed with ZA and Denosumab. We believe that ZA should be the bisphosphonate of choice in pediatric HCM with rhabdomyosarcoma, while Denosumab may be another option in ZA-refractory cases.