Aneuploidy is defined as uneven sets of chromosomes in cells, that is chromosome numbers that deviate from the exact multiples of the haploid chromosome number (which is 23 in humans). First discovered and recognized as a factor for developmental failure over 100 years ago, aneuploidy has emerged as a prevalent genome alteration in human cancer, with nearly 90% of solid tumors exhibiting varying degrees of aneuploidy [1, 2, 3, 4]. Aneuploidy is different from chromosome instability (CIN), which can also occur in tumors but refers to the elevated rate of chromosome mis-segregation during cell division. Although CIN can cause aneuploidy, not all aneuploid tumor cells display CIN. In fact, many aneuploid tumor cells maintain stable karyotypes in culture [1,5].

Aneuploidy is acquired early in the tumor evolutionary process, and is even present in pre-cancerous neoplasms [6, 7, 8]. The degree of aneuploidy tends to increase as tumors progress. Tumor samples with higher ploidy exhibit greater degrees of aneuploidy. High levels of aneuploidy are associated with advanced tumor stages, immune evasion, and poorer prognoses [4,9, 10, 11]. In this review, we discuss the emergence and consequences of aneuploidy in tumors. We highlight recent evidence demonstrating that tumors remain addicted to aneuploidy and that aneuploidy is a cancer vulnerability, which can be exploited for cancer therapy.