Chromosomal instability (CIN) is a major driver of tumor evolution and it is central to processes such as metastasis, drug resistance, and immune evasion. The relationship between CIN and cancer is complex. To better understand how CIN influences tumor evolution, we aim to deconstruct the individual cellular and microenvironmental phenotypes imparted by chromosome segregation errors. These phenotypes include genomic copy number heterogeneity as well as inflammatory signaling, both of which can have distinct phenotypes on the tumor and its microenvironment. By understanding these basic processes, we aim to develop CIN-directed therapeutic strategies for the treatment of advanced cancers.