The translocation t(X;18) is currently regarded as a specific molecular marker of synovial sarcoma (SS). Recently, however, it has been reported that malignant peripheral nerve sheath tumors expressed this marker in 75% of the cases. To test independently this iconoclastic claim, a molecular analysis for the detection of the SYT-SSX fusion genes was carried out using archival material of 34 consecutive cases diagnosed as malignant peripheral nerve sheath tumors and treated in our Institute from 1998 to 2000. In four of these cases, the molecular analysis on fixed tissues was supplemented with an analysis on fresh frozen tissue. RNA extracted from formalin-fixed paraffin-embedded tissue blocks was evaluated for the presence of SYT-SSX1 and SYT-SSX2 fusion transcripts by RT-PCR. This analysis was extended to a wide variety of normal tissues simultaneously extracted and equally processed. Only two of the cases studied harbored SYT-SSX1 and SYT-SSX2 fusion transcripts, respectively. The diagnostic reevaluation of these two cases in light of the molecular data disclosed that one had the features of a monophasic SS and the other was compatible with that entity. Both of these tumors were strongly immunoreactive for bcl-2, confirming the diagnostic utility of this marker in this instance. Our results reaffirm the specificity of SYT-SSX for SS and suggest that an opposite claim made in a recent study may have been due to a faulty interpretation of the molecular results caused by a contamination of the samples.