These seemingly contradicted findings by comparing the role of HIF-1α and HIF-2α in cell culture to that in xenograft models highlights the oncogenic role of HIF-1α in ccRCC initiation, the altered HIF-1α and HIF-2α balance in tumor development, contextual genetic background, and the role of HIF-2α in regulating tumor microenvironment. This evidence concerns the gene EPAS1 and neoplasm.