Calciphylaxis, or calcific uremic arteriolopathy, commonly affects people with end-stage renal disease and carries with it a high rate of morbidity and mortality. Here, we present the unusual case of a 56-year-old woman, with extensive medical problems, who developed calciphylaxis in the presence of primary hyperparathyroidism. Our patient initially presented with bilateral, exquisitely tender thigh lesions. The diagnosis of calciphylaxis was rendered histologically by extensive calcification of the subcutaneous blood vessels. Subsequent parathyroidectomy identified the presence of a hyperactive mediastinal parathyroid adenoma, weighing 0.62 grams. Postoperatively, the patient had normalization of hypercalcemia and parathyroid hormone levels, with subsequent healing of her thigh wounds. Currently, there have been sixteen cases described in the English literature, with only nine being offered a potentially therapeutic parathyroidectomy. It is contingent upon the vigilant physician to diagnose and properly manage this difficult yet treatable condition.