We demonstrate that the cytogenetically defined translocation t(X;18)(p11.2;q11.2) found in human synovial sarcoma results in the fusion of the chromosome 18 SYT gene to either of two distinct genes, SSX1 or SSX2, at Xp11.2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acids. The N‐terminal portion of each SSX protein exhibits homology to the Kruppel‐associated box (KRAB), a transcriptional repressor domain previously found only in Kruppel‐type zinc finger proteins. PCR analysis demonstrates the presence of SYT‐SSX1 or SYT‐SSX2 fusion transcripts in 29 of 32 of the synovial sarcomas examined, indicating that the detection of these hybrid transcripts by PCR may represent a very useful diagnostic method. Sequence analysis has demonstrated heterogeneity in the fusion transcripts with the formation of two distinct SYT‐SSX1 fusion junctions and two distinct SYT‐SSX2 fusion junctions.