Synovial sarcoma diagnosis and differential diagnostic distinction from other spindle cell sarcomas may be difficult. In these cases the detection of the t(X;18) translocation by FISH and RT-PCR is diagnostically extremely helpful. This study was aimed at the question whether or not simultaneous use of both methods is required for evidence of t(X;18) translocation.Paraffin-embedded tumour specimens from 53 patients were included in the study which were considered to be possible synovial sarcomas on the basis of histological aspect and immunohistochemical profile. Detection of t(X;18) was performed using FISH and RT-PCR simultaneously. Nuclei and amplifiable RNA could be isolated from 39 of the 53 included cases (75%). In 72% of these 39 cases FISH and RT-PCR showed identical negative or positive results. The remainder of the cases (28%) showed either a typical PCR product or a positive FISH signal.In conclusions FISH could be confirmed by typical PCR products and is therefore qualified as an internal quality control. Nevertheless tumour biological and methodical reasons have an important influence on both methods. Consequently in difficult cases simultaneous FISH and RT-PCR analysis is necessary for a clear evidence of t(X;18) translocation.