The tumorigenic activity of the CD44+ and CD44−/CD133− subpopulations isolated from SW480 control or HIF-silenced cells and the tumorigenic activity of metastatic SW620 cells were markedly negatively affected, but more importantly, the tumorigenic activities were similarly abolished as a result of the silencing of either HIF-1α or HIF-2α, emphasizing the importance of both factors in the promotion of tumor growth and progression in vivo. This evidence concerns the gene CD44 and neoplasm.