About 70% of clear cell sarcomas show a balanced chromosomal translocation t(12;22)(q13;q12) which fuses EWSR1 on chromosome 22 with ATF1 on chromosome 12. The EWSRI-ATF1 fusion protein mimics the action of melanocyte stimulating hormone by activating the promoter for MiTF – the melanocyte transcription factor - which drives tumorigenesis. This translocation is not present in cutaneous melanomas. A second translocation t(2;22)(q32.3;q12) resulting in the fusion of EWSR1 and CREB1 has been described in clear cell sarcoma-like tumor of gastrointestinal tract. EWSR1-CREB1 rearrangement is not unique to clear cell sarcomas and has been described in pulmonary myxoid sarcoma. The EWSR1 fusions with both partner genes (ATF1 and CREB1) have also been reported in angiomatoid fibrous histiocytomas. The image shows a clear cell sarcoma with numerous touton-type multinucleated giant cells surrounded by spindle or fusiform cells with clear cytoplasm.