Human cancers harbor great numbers of genomic alterations. One of the most common alterations is aneuploidy, an imbalance at the chromosome level. Some aneuploid cancer cell populations show varying chromosome copy number alterations over time, a phenotype known as 'chromosomal instability' (CIN). Chromosome segregation errors in mitosis are the most common cause for CIN in vitro, and these are also thought to underlie the aneuploidies seen in clinical cancer samples. However, CIN and aneuploidy are different traits and they are likely to have distinct impacts on tumor evolution and clinical tumor behavior. In this opinion article, we discuss these differences and describe scenarios in which distinguishing them can be clinically relevant.