BACKGROUND: Calciphylaxis is an uncommon disorder characterized by calcification of cutaneous arterioles and subsequent skin necrosis. The spectrum of lesions ranges from subcutaneous nodules to frank ulceration of the skin and underlying tissue. The atypical ulcers are exquisitely painful and refractory to standard healing therapy. Typically, calciphylaxis affects patients with end-stage renal disease and altered calcium/phosphate metabolism. Apligraf is a bilayered bioengineered skin substitute containing growth factors that has been approved for use in the treatment of diabetic and venous ulcers. Its use has also been reported in the treatment of ulcers due to vasculitis, sarcoidosis, and drug-induced lesions. METHOD: We present a 44-year old male with alcoholic cirrhosis and transient acute renal failure who developed large ulcers on both lower extremities. The lesions were treated with standard local wound care and repeated debridement without any improvement over a six-week period, following which, Apligraf was applied to both lesions. RESULTS: The patient experienced pain-relief and complete closure of the lesions over a 2-week period with stable wound coverage over 18 month follow-up. CONCLUSION: Refractory ulcers due to calciphylaxis may be treated with Apligraf which provides alleviation of pain, closure of the chronic wounds, and decreased cost of chronic wound care.