Introduction. Calciphylaxis is a very complicated disease that usually presents in patients with end-stage renal disease (ESRD). Treatment for calciphylaxis is not well standardized and typically involves a multidisciplinary approach. One of the common medications used in calciphylaxis treatment is sodium thiosulfate (STS). However, its intravenous injection is associated with multiple side effects. Case Report. The authors present a case report of an intralesional injection of STS followed by a literature review of the common treatment modalities and possible further use of intralesional injections. A 51-year-old man with ESRD on peritoneal dialysis presented with a right calf biopsy-proven calciphylaxis lesion measuring 3.1 cm x 3.9 cm. About the same time, he had Pseudomonas-associated peritoneal catheter peritonitis. The calciphylaxis lesion was treated with bimonthly intralesional injections of STS. The lesion had a complete resolution by week 9. Conclusions. The authors believe a higher local concentration of STS leading to a faster resolution and requiring less frequent injections needs to be further evaluated. Following additional studies, they also propose a greater use of intralesional STS injections in a select set of patients in the future.