This article highlights recent advances in the molecular structure and function of proteins that are activated or created by chromosomal abnormalities and discusses their possible role in tumor development. The molecular characterization of these proteins has revealed that tumor-specific fusion proteins are the consequence of most chromosome translocations associated with leukemias and solid tumors. An emerging common theme is that creation of these proteins disrupts the normal development of tumor-specific target cells by blocking apoptosis. These insights identify these chromosomal translocation-associated genes as potential targets for improved cancer therapies.