On the basis of the expression pattern of HIF1α, ccRCC tumors can be divided into two subtypes: H2 ccRCC tumors that express HIF2α but not a functional HIF1α protein, and H1H2 ccRCC tumors that express both HIF1α and HIF2α protein.2, 22 Given the evidence that HIF1 functions as a tumor suppressor, an important question that has not been addressed is how H1H2 ccRCC tumors tolerate HIF1α protein expression. This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.