Investigations into the molecular alterations in sarcomas have made substantial progress during the past decade. Classical linkage analysis and the direct sequencing of chromosomal translocation fusions have identified candidate genes in many different sarcomas. A large group of these genes participate in signal transduction pathways and represent potential sites of disease intervention with targeted therapies. This review will discuss five types of sarcoma that display aberrant tyrosine kinase pathway signaling: gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, congenital fibrosarcoma and mesoblastic nephroma, dermatofibrosarcoma protuberans, and desmoplastic small round cell tumor; one sarcoma predisposition syndrome with specific dysregulation of the ras pathway--neurofibromatosis--will also be discussed.