The FUS gene encodes an RNA-binding protein, the C-terminal end of which is involved in protein and RNA binding and which appears to be involved in transcriptional activation with its N-terminal end. It shares distinct characteristics with EWSR1 and TAF15 which together with FUS are frequently referred to as the FET family of proteins. FUS gene rearrangements have been shown to be involved in both solid tumors and leukemias fusing the N-terminal end of FUS to various fusion partners. The most frequent translocation involving the FUS gene region is t(12;16)(q13.3;p11.2). Occurring in over 90% of myxoid liposarcomas, the FUS-DDIT3 fusion protein is regarded as being consequential for the development of myxoid liposarcomas by acting as an abnormal transcription factor and thus deregulating FUS-DDIT3 target genes. Differential diagnosis of liposarcomas and accurate classification, the latter being especially important with regard to appropriate treatment and prognosis, are often problematic. Therefore, detection of FUS rearrangements via in situ Hybridization analysis is a valuable tool to confirm the histopathological diagnosis of myxoid liposarcoma.