In humans, female cells have 22 pairs of chromosomes, an active X chromosome (Xa) and an inactive X chromosome (Xi), whereas male cells have 22 pairs of chromosomes, an X chromosome and a Y chromosome. Cells derived from human cancers often are aneuploid and contain altered numbers of chromosomes, which have frequently undergone rearrangements from the canonical state. However, when grown in cell culture, both female and male cells (and also both normal and cancer-derived cells) can evolve into a ‘de-sexualized state’ that contains a single X chromosome. In these de-sexualized cells, the X chromosome frequently undergoes a duplication, which is followed by the duplication of one full set of autosomal chromosomes to produce an X:A=2:3 state that contains 68 chromosomes on average (as opposed to 46); this state appears to have been repeatedly selected for in cell culture conditions.