To improve on current cancer therapies, which attack cells on the basis of their proliferative tendencies, much effort has been devoted to a search for properties of tumor cells that are tumor-specific rather than proliferation specific. Evidence from molecular genetic studies suggests, however, that most tumors may lack such properties. An alternative approach to therapy is described that is based on a property known to characterize the majority of human tumors; viz., a monoclonal origin. The strategy requires the prophylactic induction in tissues of mosaicism for genes dictating sensitivity or resistance to chemotherapeutic agents, and exploits the observation that any clone of cells arising in a mosaic tissue must inevitably differ from some other cells in the mosaic. Recent advances in genetic technology imply that the strategy is likely to be testable soon in animals, and that it may significantly improve the results of cancer therapy when a technology safe and efficient enough for its human implementation becomes available.