When compared to a reference population, several large epidemiological studies with long-term follow-up have reported a three- to five-fold increased risk of neoplasia amongst patients who have received organ transplants, with an incidence curve that rises in a linear fashion with time. The relationship between the immune system and cancer is complex. The ability to discriminate “self” from “non-self” is one of the central roles of the immune system. Since tumors arise from transformation of host cells, it is not surprising that some aspects of tumor immunity resemble autoimmunity. The immune response to tumors shares aspects of both self- and non-self-immune recognition. What accounts for the apparent failure of immunity? In this review article, we address the role of the self/non-self-survey in the immune response to tumors, we describe mechanisms of immune surveillance against tumor cells, and we discuss models of ignorance, tolerance and tumor evasion of the immune response. The overall aim of the article is to demonstrate the scope for prevention of cancer in individuals at increased risk of developing malignancy due to immune compromise. Interventional strategies may involve the use of pro-differentiation agents such as retinoids, modifiers of polyamine biosynthesis or inhibitors of cyclooxygenase isozymes.