The cancer cell fusion theory has emerged in the last few years as a critical yet under-recognised mechanism contributing to tumour progression and metastasis. This chapter revisits its historical foundations and explores the cellular and molecular mechanisms that underpin fusion events. The resulting tumour hybrid cells (THCs) display enhanced migratory and invasive properties and chemoresistant properties, together with profound immunomodulatory capacities. These hybrids often express immune cell markers and stem-like features, enabling them to evade immune surveillance and adapt to hostile microenvironments. Recognition of cell fusion as a driver of tumour evolution challenges classical models of metastasis and highlights the urgent need to identify biomarkers and therapeutic targets associated with fusion-derived hybrids.