Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder that is caused by a mutation in the NF1 gene. Hallmark characteristics include dermal neurofibromas, café-au-lait spots, and learning disabilities. In approximately 25% of NF1 cases, plexiform neurofibromas, or peripheral nerve sheath tumors (PNSTs) that involve large segments of nerve sheath and nerve root, can form, of which a small percentage become malignant (MPNST). Most MPNSTs are composed of spindled neoplastic cells, and they can resemble other spindle-cell sarcomas, including leiomyosarcoma and monophasic synovial sarcoma. Histological diagnosis of MPNST is not always straightforward, and various immunohistochemical and molecular adjuncts can be critical in establishing a correct diagnosis. One example of genetic testing is the assay for the t(X;18) chromosomal translocation, which has been found to be common in synovial sarcomas. The aim of this study was to determine whether MPNSTs contain the t(X;18) chromosomal translocation. To detect the t(X;18) translocation product, SYT-SSX, total RNA was extracted from frozen archival tumors (15 dermal neurofibromas, 4 plexiform neurofibromas, and 7 MPNSTs) using Trizol. The RNA was then subjected to reverse-transcriptase polymerase chain reaction (RT-PCR) to specifically amplify SYT-SSX. None of the dermal neurofibromas, plexiform neurofibromas, or MPNSTs analyzed were positive for SYT-SSX mRNA. The results indicate that the t(X;18) translocation is absent in neurofibromas and is not a marker for MPNST in patients with NF1.