Calciphylaxis is a rare but serious condition characterized by the calcification and thrombosis of small blood vessels, predominantly affecting patients with end-stage renal disease (ESRD). Diagnosis can be challenging due to overlapping features with other vascular conditions, such as warfarin-induced skin necrosis (WSN). We present a case of a patient with ESRD and typical risk factors—peritoneal dialysis, hyperparathyroidism, and warfarin use—who exhibited classic skin findings suggestive of calciphylaxis. However, two skin biopsies were inconclusive. Management involved addressing the patient's calciphylaxis risk factors, optimizing dialysis, and initiating sodium thiosulfate therapy. The case was further complicated by the need to replace warfarin, as current guidelines only approve its use for patients with mechanical heart valves.