The DDIT3 gene encodes for a stress-induced dominant-negative inhibitor of the transcription factors C/EBP and LAP. DDIT3 is consistently rearranged in myxoid liposarcomas (MLS). The most frequent translocation involving the DDIT3 gene region is t(12;16)(q13.3;p11.2) and occurs in about 90% of patients with MLS. The rearrangement results in a fusion gene comprising the 5´part of the FUS (fused in sarcoma) gene, located in 16p11.2, and the complete coding region of the DDIT3 gene. The FUS-DDIT3 fusion protein acts as an abnormal transcription factor and development of myxoid liposarcomas is thus regarded as a consequence of deregulated 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 DDIT3 rearrangements via FISH analysis is a valuable tool to confirm the histopathological diagnosis of myxoid liposacrcoma.