Soft tissue sarcomas are a versatile group of tumors with a proposed origin from mesenchymal stem cells. During recent years, the molecular biologic mechanisms behind the histogenesis of these tumors have become clearer. In addition to translocations and other genomic changes, epigenetic mechanisms have been shown to be greatly involved in the histogenesis of sarcomas as well as other cancers. Even though the molecular mechanisms behind sarcomas appear to be more complex than previously expected, epigenetic mechanisms bring new opportunities and means for the treatment of these complex diseases.