Carcinogenesis can be initiated in adult stem cells, suggesting that tumours arise as a consequence of stem-cell dysfunction. In the fruitfly, cancer arises in stem cells that fail to undergo asymmetric cell division. In flies and mammals, a specific regulation of the endocytic trafficking machinery allows stem cells to self-renew and generate the differentiating cells required to form and maintain mature organs. We review recent findings suggesting that an understanding of the relationship between endocytosis, asymmetric cell division, stem cells and cancer will be crucial to unravel the cell biological basis of tumourigenesis.