Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma of chondroblastic origin that occurs primarily in adults. The tumor is characterized by recurrent chromosomal translocations resulting in fusions of the NR4A3 gene to various N-terminal partners including EWSR1, RBP56, TCF12, and TFG. NR4A3 is a member of the steroid/thyroid receptor superfamily and acts as a transcriptional activator. The resulting chimeric proteins contain N-terminal parts of the various partners fused to the entire coding sequence of NR4A3. The most frequent reciprocal translocation is t(9;22)(q22.3- q31;q12.2) found in about 70% of EMC generating a EWSR1-NR4A3 fusion gene in which the 3'-terminal part of EWSR1 is replaced by the entire NR4A3 gene. EMC is histologically characterized by a mixture of cellular and myxoid stromal components, making it difficult to distinguish it from other benign or malignant mesenchymal tumors. Since chromosomal translocations of EWSR1 are found in several different neoplasias while NR4A3 rearrangements have been exclusively detected in EMC, assessment of NR4A3 rearrangements by Fluorescence in situ Hybridization might represent a helpful tool for the differential diagnosis of EMC.