The main function of the mammalian immune system is to monitor tissue homeostasis, to protect against invading or infectious pathogens and to eliminate damaged cells. Therefore, it is surprising that cancer occurs with such a high frequency in humans. Recent insights that have been gained from clinical studies and experimental mouse models of carcinogenesis expand our understanding of the complex relationship between immune cells and developing tumours. Here, we examine the paradoxical role of adaptive and innate leukocytes as crucial regulators of cancer development and highlight recent insights that have been gained by manipulating immune responses in mouse models of de novo and spontaneous tumorigenesis.