BUB1 is an activator of the spindle assembly checkpoint, and its altered expression promotes tumorigenesis, which is associated with aneuploidy and chromosome missegregation. Ricke and colleagues generated knock-in mice expressing a kinase-dead BUB1 mutant, which was expressed at normal levels. Surprisingly, these mice did not develop tumours and were not more susceptible to carcinogenesis (unlike mice with altered expression of BUB1), despite aneuploidy and errors in chromosome segregation. This indicates that the type of chromosome instability induced in these knock-in mice does not promote tumorigenesis and so further investigation is required.