The primary genetic lesion associated with ccRCC is loss or inactivation of the tumor suppressor gene, VHL. The VHL gene encodes the Von-Hippel Lindau E3 ubiquitin ligase that is responsible for proteasome mediated degradation of the hypoxia inducible factors HIF-1α and HIF-2α [2, 3]. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.