OBJECTIVE: To describe an allopurinol desensitization that failed on the first attempt but was successful on the second attempt, resulting in the management of crippling tophaceous gout. CASE SUMMARY: A 64-year-old white man with a history of gouty nephropathy requiring hemodialysis developed a severe cutaneous reaction from exposure to allopurinol. The first desensitization attempt was unsuccessful, and the gouty nephropathy caused chronic cellulitus and urate microcrystal deposition on the patient's hands and feet. Continuous ambulatory peritoneal dialysis and hemodialysis were used to treat the patient's severe symptoms and increase uric acid clearance. This method, however, was ineffective. Severe tissue ischemia, requiring bilateral below-the-knee amputations, prompted the second desensitization attempt four years later. The second attempt, administered differently and with more caution, was successful and did not cause further complications. DISCUSSION: Allopurinol is the only agent available to effectively reduce uric acid concentrations in those who are over-producers. Hypersensitivity-type reactions have been reported with its use, and desensitization is the only viable therapeutic option. Few cases of desensitization to allopurinol have been reported in the literature. This article describes a failure and a subsequent success in desensitization to allopurinol. CONCLUSIONS: Although desensitization to allopurinol poses potential risks, the benefits can outweigh the risks of therapy. Desensitization requires close monitoring; if failure does occur, subsequent attempts can be successful, as this case report demonstrates.