Background: Calciphylaxis in a nondialysis patient is a rare condition and is characterized by calcific deposition in tissue. We present a case of calciphylaxis in a nondialysis patient who was diagnosed by clinical presentation and skin biopsy and was treated with sodium thiosulfate with improvement of skin lesions. Case: A 43-year-old female with type 2 diabetes and atrial fibrillation taking oral anticoagulation medication presented with reddish drainage from the right buttock. On physical examination, a large perirectal abscess overlying necrosis was found. She also developed acute kidney injury with creatinine of 3.7 mg/dL at peak from 0.8 mg/dL at baseline. She received antibiotics intravenously and wound debridement. During hospitalization, she developed areas of numerous painful erythematous lesions with central dusky necrosis on bilateral lower extremities. Punch biopsy was done, which initially revealed small-vessel vasculitis. However, those lesions did not respond to steroid therapy. A second biopsy was done showing extensive fat necrosis and medial calcification of vessel walls consistent with calciphylaxis. She was treated with high-flow oxygen and sodium thiosulfate intralesionally and intravenously for 6 months. The lesions remarkably reduced in size and were less painful on follow-up. Conclusion: High-dose oxygen and sodium thiosulfate could potentially be effective treatments for calciphylaxis in nondialysis patients.