Aneuploidy, metastasis formation, and drug resistance are major issues to overcome in most cancers. If there exists common underlying proceedings for the formation of these phenomena is still unknown. The searching and thereby better understanding of causal mechanisms could promote the generation of drugs targeting the ultimate cause of these cancer promoting events. The merging of a cancer cell with another cancer cell or normal cell could be one explanation how cancer cells could gain advantageous properties and escape eliminating cell fates thereby foster cancer progression. This chapter summarizes how cell-cell fusion could directly be involved in the pathogenesis of cancer and which often cancer associated mechanisms, like viral infections or chronic inflammation, are hitherto proposed to trigger cell fusion in cancer context.