Alterations in chromosomal content and structure are a defining feature of several pathological states, including nearly all cancer types. Despite this, very little is known about the mechanisms that cause these aberrations to accumulate, and what their functional significance is to disease. Our lab is interested in defining the mechanisms that cause chromosomal instability in cancer. To do this we take the approach of characterising the acute genomic alterations that occur as a result of specific chromosomal instability mechanisms (for example replication stress, mitotic dysfunction) using single cell genomics and cell biology. In this way we aim to ultimately track backwards from cancer chromosomal alterations to decipher their origin. In this talk I will give an overview of three studies we have undertaken to address this question using this approach.