Although the exact mechanisms mediating the initiation of autoimmune diseases are unknown, sequence similarity between infectious agents and self-proteins (epitope mimicry) has been proposed as the main trigger mechanism. Interestingly, this mechanism of epitope mimicry may also evoke potent tumor immunity. Indeed, experimental data support a beneficial role of autoimmunity in some patients with cancer. Additionally, autoimmunity induced via vaccination with xenogeneic antigens was found to be effective. Thus, the ability to manipulate the immune system via immunologic cross-reactions should have important potential in both preventive and therapeutic strategies for cancer. This strategy may down the friendly established relationship between tumor tissues and the cells of the immune system.