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Zoledronic acid is reported to significantly reduce skeletal morbidity and prolong time to bone lesion progression in patients with bone metastases from various malignant tumors including renal cell carcinoma. Due to renal uptake and elimination of zoledronic acid, however, it is difficult to control dose alignment in patients with kidney dysfunction. We reviewed significance of hemodialysis and monitoring of serum creatinine and calcium in patients with ESRD. (Cases) We experienced two cases of end-stage renal disease (ESRD) with bone metastases from advanced renal cell carcinoma. Zoledronic acid was given to both patients by 15 minutes intravenous infusion followed by hemodialysis 24 hours later. Systemic cytokine infusion and oral thalidomide were also given to both patients. Level of serum calcium reduced in one case two weeks later, and treated by calcium administration. No other adverse effects were noted for more than six months of combination therapy. Both cases maintained stable disease not only for bone metastases but also for the systemic condition without any organ failure. Even in patients under maintenance hemodialysis, zoledronic acid can be given with certain safety and efficacy by hemodialysis 24 hours after administration and intense monitoring of serum calcium level. We think this is the first report of zoledronic acid treatment to ESRD patients with bone metastases from malignant tumors.