Many types of sarcomas are characterized by specific chromosomal translocations that result in the production of novel chimeric genes. Detection of these fusion genes could be a sensitive molecular diagnostic assay. However, to the authors' knowledge there have been few systemic comparisons between the current histopathologic diagnosis and the presence or absence of particular fusion genes in patients with adult soft tissue sarcomas (STSs).Total RNA was extracted from 75 cases of STS and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of a variety of fusion transcripts. The results of the molecular assay were compared with standard histopathologic diagnoses.Of the 18 tumors diagnosed as synovial sarcoma, 17 (94%) expressed SYT-SSX chimeric transcripts. All nine myxoid liposarcomas were positive for FUS-CHOP fusion transcripts. Of the four cases of Ewing sarcoma, two had an EWS-FLI1 fusion transcript and one had an EWS-ERG fusion transcript. A clear cell sarcoma had a EWS-ATF1 fusion transcript. None of 19 cases of malignant fibrous histiocytoma nor 3 leiomyosarcomas contained a fusion transcript. Three cases with an initial diagnosis other than synovial sarcoma expressed a SYT-SSX fusion transcript. A review of the slides and additional examination showed that a diagnosis of synovial sarcoma was appropriate for these cases. There was a trend for biphasic synovial sarcoma to contain the SYT-SSX1 fusion.The authors believe RT-PCR assay for the detection of a specific fusion gene provides a useful tool for confirmation of the diagnosis of adult STS in diagnostically difficult cases and in retrospective studies.