The radiation of animals in the so-called Cambrian ‘explosion’ was a late event in Earth history and its drivers remains unresolved. Environmental drivers, such as an increase of atmospheric oxygen, and ecological drivers, like the innovation of predation, have been associated to the Cambrian explosion while developmental drivers remain largely unexplored. Here, I will present clues from tumor biology demonstrating the necessity for multicellularity – albeit in its unwanted form of tumors – to manage cell responses associated with low oxygen (hypoxic). Hypoxic cell responses can promote the immature phenotype of cells (stemness), which is essential for all tissue renewal – also in healthy animal tissue. The tumour analogy results in new questions regarding animal evolution: How can we renew tissue despite an oxic setting and how did we adapt into the oxic setting? I will take you through my ideas of the cellular tools that allowed bilaterian animals to enter into the oxic realm, and there diversify during the Cambrian. That tissue requires hypoxia for stemness has bearing, I claim, on what it takes for large life to evolve also on other planets.