Fluorescence in situ hybridization (FISH) evaluations of chromosome 18 were performed in synovial sarcoma, hemangiopericytoma, and mesothelioma. Each case was evaluated with centromeric and whole chromosome paint probes. The synovial sarcomas had t(X;18) cytogenetically, but the FISH evaluator was blinded to the cytogenetic results and to the histopathologic diagnosis. The FISH analyses were consistent with chromosome 18 translocation in 6 of 7 synovial sarcomas, 0 of 3 hemangiopericytomas, and 0 of 1 mesothelioma. These findings support the use of FISH in the diagnosis of synovial sarcoma.