This case report examines two rare mechanisms of acute renal failure in a patient with metastatic melanoma treated with high-dose vitamin C. The first is oxalate nephropathy, which is an uncommon but known complication of high-dose vitamin C therapy in naturopathic medicine. The second is due to melanuria and renal melanosis, which has been described in metastatic melanoma; however, acute renal failure requiring renal replacement therapy has not been reported previously.