The inappropriate accumulation of HIF-1α and HIF-2α, caused by biallelic mutations in the von Hippel-Lindau (VHL) gene observed in the majority of clear cell RCC cases, is considered a pivotal step in RCC tumorigenesis.8 Neuroendocrine tumors (NETs) are associated with some rare familial syndromes, which result from mutations in genes linked to the PI3K-AKT-mTOR pathway, including Multiple Endocrine Neoplasia-1 (MEN1),9 Neurofibromatosis-1 (NF1),10 VHL11 and PTEN.12 Clinical efficacy of rapamycin analog (rapalog), everolimus, has been demonstrated in RCC and certain NETS. The gene discussed is PTEN; the disease is renal cell carcinoma.