A 76-year-old man had biopsy-proven acute tubular necrosis (ATN) after intravenous administration of 3 doses of 60 mg of pamidronate (Aredia) over a 2-week period. Pamidronate was given to treat hypercalcemia of unknown etiology. Other potential causes of acute renal failure were excluded with appropriate investigations. The patient's preexisting renal impairment in the context of high-doses of pamidronate might have been a potentiating factor for nephrotoxicity. The ATN encountered in this patient resolved; however, short-term hemodialysis was needed. To the best of our knowledge, this is the first reported case of short-term, high-dose pamidronate-induced ATN in the absence of concomitant nephrotoxins. Although necrotic and apoptotic cell death after bisphosphonate administration has been seen in a variety of cells, the exact mechanism of nephrotoxicity is unknown. This report presents a case of pamidronate-induced ATN and discusses the potential mechanisms of bisphosphonate-induced nephrotoxicity.