Chromosomal Instability (CIN) is a common occurrence in solid cancer associated with poor survival in patients. A significant percentage of these tumours show abnormal chromosome numbers with near-triploid or tetraploid phenotype exhibiting numerical CIN (nCIN). nCIN is caused mainly due to deregulation of cell cycle proteins. Early Mitotic Inhibitor 1 (Emi1) is a cell cycle protein that regulates the activity of E3 ubiquitin ligase, Anaphase Promoting Complex/Cyclosome (APC/C), which targets many proteins for degradation during cell cycle. Emi1 is overexpressed in many solid tumours but not blood cancers. In vivo overexpression of EMI1 in mouse models causes more penetrant and metastatic tumours. Supporting the in vivo model, human breast cancer tissues show significantly high expression of Emi1 with increasing tumour grade. Additionally, Emi1 expression from breast cancer TCGA data strongly correlated with the chromosomal instability signature than many of the well-established genes known to promote CIN phenotype. To understand the mechanisms of CIN due to Emi1 overexpression, we overexpressed Emi1 in HeLa cells expressing GFP-tagged histone protein to monitor the cells during mitosis by live cell imaging. HeLa cells overexpressing Emi1 show CIN following delays in both chromosome alignment at the metaphase plate and, subsequently, anaphase onset (p=0.0008 and p=0.0028). Altogether, the significant increase in CIN phenotypes and abnormal mitoses such as anaphase bridges/lagging chromosomes, mitotic arrest and cell death indicate that Emi1 overexpression actively drives tumorigenesis. These novel mechanistic insights have important clinical implications.