A defining feature in over 2/3rds of all solid tumours is the continual loss and gain of whole and/or small parts of chromosomes. This chromosome instability (CIN), is strongly implicated in tumour initiation, progression, chemoresistance and poor patient prognosis. A primary cause of CIN is incorrect mitotic cell division, whereby missegregation of chromosomes creates daughter cells with fragmented and or unequal chromosome numbers. Although CIN is a common feature of cancer, somatic mutations in the mitotic (spindle) checkpoint machinery are rare, leading to speculation that CIN is caused by the premature activation of the mitotic exit pathway. Entry into mitosis and progression up to metaphase is primarily driven by Cdk1, which directly and indirectly drives >32,000 phosphorylation events. In parallel, MASTL represses the activity of the major mitotic phosphatases, thereby ensuring sites remain phosphorylated during mitosis. Loss of MASTL results in the premature and precocious activation of phosphatases, which results in multiple mitotic defects including the missegregation of chromosomes and failed cytokinesis resulting in the formation of aneuploid daughter cells. These defects occur despite the spindle assembly checkpoint remaining active, indicating that MASTL is downstream of this critical surveillance system. Therefore, understanding how MASTL and phosphatases are regulated during mitosis is essential for gaining a better understanding of how defective mitosis occur. To this end, we recently demonstrated that the phosphatase PP1 is associated with MASTL during mitotic exit and is capable of partially dephosphorylating and deactivating MASTL. Mathematical modelling showed that PP1 is required for triggering the initial dephosphorylation of MASTL, releasing PP2A inhibition, which completes MASTL and Cdk1 substrate dephosphorylation. This data provides a unifying theory where both PP1 and PP2A are required for efficient deactivation of MASTL, thereby establishing a bistable switch that drives mitotic exit, the correct division of daughter cells and maintenance of genomic stability.