Calciphylaxis is a rare and severe complication characterized by calcification of arterioles and capillaries in the dermis and subcutaneous adipose tissue that leads to ischemia, necrosis, and painful skin lesions in patients with end-stage renal disease (ESRD). It is also known as calcific uremic arteriolopathy. Calciphylaxis occurs most commonly with the ESRD with skin ulceration as a predominant presenting feature. Calcium-phosphorus dysregulation in dialysis patients are traditionally considered as a risk factor for the development of calciphylaxis. The involvement of an integrated interdisciplinary and multifaceted approach is key to the success of the calciphylaxis treatment. We present a case of a 51-year-old female with ESRD on home hemodialysis who developed calciphylaxis, which was successfully managed with increasing dialysis prescription, diligent wound care, and sodium thiosulfate infusion. Management of calciphylaxis in a patient receiving home hemodialysis has never been reported as per the review of the literature. Calciphylaxis is a sporadic disease, frequently encountered in the patients undergoing hemodialysis and carries a very grave prognosis. Current treatment is rarely effective, so preventive strategies play an important role by modifying the risk factors that promote the development of calciphylaxis.