Of patients with cryptorchidism, 5% have no palpable gonad. Physical examination or scrotal exploration demonstrates tissue nubbins or small nodules that constitute the vanishing testis syndrome. At the University of Chicago Hospitals (Chicago, IL; 2004-2008), 30 surgical pathology specimens from 29 patients with this clinical diagnosis underwent scrotal exploration. Histologic and immunohistochemical comparison was done with 7 fetal testes, 8 surgically removed nonneoplastic testes, and 2 cryptorchid testes. Routine histologic studies showed no seminiferous tubules in 18 cases (60%), fibrosis in all (100%), calcifications in 16 (53%), and hemosiderin deposits in 9 (30%). In 12 cases with seminiferous tubules (40%), there were Sertoli cells only. Scrotal exploration in such cases is clinically driven and results in the removal of any tissue present. Although published studies suggest the risk for future tumor development is low, possibly absent, the definitive removal of a testicle is established by an awareness of the histologic spectrum exhibited by testicular remnants.