We report the development of a reverse-transcriptase polymerase chain reaction assay that detects (in paraffin-embedded, formalin-fixed tissue) the SYT-SSXchimeric RNA transcript resulting from the t(X;18) of synovial sarcoma. The primers chosen detect both of the SSX1 and SSX2 partners, and the target sequence is small enough (87 base pairs) to be reliably detected in archival and variably processed consultation material. To demonstrate its usefulness, we applied it to 14 problematic cases, including spindle cell tumors of the thoracic region, of the neck, and of subcutaneous tissue. For instance, we show that, depending on the location, synovial sarcoma can mimic malignant solitary fibrous tumor, the spindle epithelial tumor with thymus-like differentiation, or skin adnexal tumors. Molecular detection of the SYT-SSX chimeric RNA should allow the reclassification of difficult cases in which the morphologic features overlap different entities or in which tumor nosology is still evolving.