Chromosomal instability and aneuploidy are similar concepts but not synonymous. CIN is the process that leads to chromosome copy number alterations, and aneuploidy is the result. While CIN and resulting aneuploidy often cause growth defects, they are also selected for in cancer cells. Although such contradicting fates may seem paradoxical at first, they can be better understood when CIN and aneuploidy are assessed separately, taking into account the in vitro or in vivo context, the rate of CIN, and severity of (...) the aneuploid karyotype. As CIN can only be measured in living cells, which proves to be technically challenging in vivo, aneuploidy is more frequently quantified. However, CIN rates might be more predictive for tumor outcome than assessing aneuploidy rates alone. In reviewing the literature, we therefore conclude that there is an urgent need for new models in which we can monitor chromosome mis-segregation and its consequences in vivo. Also see the video abstract here: https://youtu.be/fL3LxZduchg Chromosomal Instability leads to chromosome mis-segregations, creating different forms of aneuploidy over time. Some forms of aneuploid are detrimental, while others are favorable to cell growth. CIN is often studied in vitro, it is rarely studied in vivo, despite its role in both cancer and aging. (shrink)