At present, the hallmark feature of ESFT is the presence of non-random translocations leading to the fusion of the EWS gene with one of several members of the ETS family of transcription factors [19] (Table 20.2). The most frequent of these translocations is t(11;22)(q24;q12), which is detected in 90–95% of cases [20,21]. This leads to in-frame fusion of EWS at 22q12 to FLI1 at 11q24 and the formation of EWS-FLI1 on der(22) comprising the 5 end of EWS and the 3 end of FLI1 [21] (Figure 20.1). The fusion gene encodes an oncoprotein consisting of the N-terminal domain of EWS and the DNA-binding domain of FLI1