We discuss the pathophysiology of xanthine stones, the use of allopurinol in patients with HPRT deficiency experiencing uric acid overproduction, the consequences of allopurinol overdosing, the challenges associated with the combined diagnoses of Lesch-Nyhan syndrome and Factor V Leiden, and the myriad medical and surgical managements for urolithiasis associated with Lesch-Nyhan syndrome. This evidence concerns the gene F5 and Lesch-Nyhan syndrome.