We report the case of a 59-year-old woman with end-stage renal disease who presented with bilateral medial calf tenderness and subsequent development of a large necrotic plaque that was proven at biopsy to be calciphylaxis. A radionuclide bone scan contributed to management by helping establish the diagnosis. Calciphylaxis is a highly morbid small vessel vasculopathy encountered in patients on hemodialysis. Early recognition and proper management may improve outcomes.