Endoreduplication (also referred to as endoreplication or endocycling) is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreduplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity.[1][2][3][4] Examples of endoreduplication characterised in arthropod, mammalian, and plant species suggest that it is a universal developmental mechanism responsible for the differentiation and morphogenesis of cell types that fulfill an array of biological functions.[1][2] While endoreduplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that polyploidy can be detected in the majority of plant tissues.[5] Polyploidy and aneuploidy are common phenomena in cancer cells.[6] Given that oncogenesis and endoreduplication likely involve subversion of common cell cycle regulatory mechanisms, a thorough understanding of endoreduplication may provide important insights for cancer biology.