Many types of sarcomas are characterized by specific chromosomal translocations that appear to result in the production of novel, tumor-specific chimeric transcription factors. Many of these show striking similarities: the emerging picture is that the amino-terminal domain of the fusion product is donated by the Ewing's sarcoma gene (EWS) or a related member from the same gene family, whereas the carboxy-terminal domain often consists of a DNA-binding domain derived from one of a number of transcription factors. Given the observation that the different translocation partners of the EWS protooncogene are associated with distinct types of sarcomas, the functional consequence of fusing EWS (or a related family member) to a different DNA-binding domain can only be understood in the context of functional studies that define the specificity of action of the different fusion products. An understanding of the molecular structure and function of these translocations provides new methods for diagnosis and novel targets for therapeutics.