A growing body of research is addressing how pathways that are dysregulated during tumorigenesis are linked to innate immune responses, which can contribute to immune surveillance of cancer. Components of the innate immune system that are localized in tissues are thought to eliminate early neoplastic cells, thereby preventing or delaying the establishment of advanced tumours. This Review addresses our current understanding of the mechanisms that detect cellular stresses that are associated with tumorigenesis and that culminate in the recognition and, in some cases, the elimination of the tumour cells by natural killer cells and other lymphocytes that express natural killer cell receptors.