Calciphylaxis is a severe "vascular ossification-calcification," associated with a very high mortality rate that involves arterial wall, venular wall, and nerves resulting in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscles. Sodium thiosulfate has recently been used as a novel treatment option for calciphylaxis because of its dual role as an antioxidant and a chelator. Multiple case reports demonstrated that such therapy has resulted in pain relief and healing of skin ulceration. We report a case of calciphylaxis of large severity that had an ambiguous response to sodium thiosulfate treatment (improvement of symptomatology and skin lesions, improvement of blood parameters, worsening of general conditions, and consciousness until death).