Instead of exploiting the differences between normal and cancer cells, seemingly unrelated anticancer modalities (from immunotherapy to hormones) exploit (a) the differences between various normal tissues and (b) tissue-specific similarities of normal and cancer cells. Although these therapies are successfully used for years to treat leukaemia and cancer, their unifying principles have never been explicitly formulated: namely, they are aimed at differentiated cells and normal tissues and target both normal and cancer cells in a tissue-specific manner. Whereas tiny differences between cancer and normal cells have yet to be successfully exploited for selective anticancer therapy, numerous tissue-specific differences (e.g. differences between melanocytes, prostate, thyroid and breast cells) provide a means to attack selectively that exact tissue that produced cancer. Despite inherent limitations, such as fostering resistance and dedifferentiation, tissue-selective therapy have enormous potentials to control cancer.