Molecular mechanisms regulating tissue changes from benign to invasive and finally to metastatic neoplasia is an area of growing scientific interest. Malignant transformation in epithelial tumors is Cycloheximide described as epithelial-to-mesenchymal transition. EMT is defined as a sequence of protein modifications and transcriptional events in response to a certain set of extracellular stimuli leading to a stable, but sometimes reversible, cellular change. Multiple molecular mediators of EMT have been described in carcinomas. The list of EMT pathways includes nuclear factor-kappa B, AKT/mammalian target of rapamycin axis, mitogen-activated protein kinase, beta-catenin, protein-kinase C and others. However, expression of markers linked to EMT does not support EMT as a biological event in STSs. Moreover, the markers linked to EMT have clearly defined roles in tumor biology that are distinct from EMT, and the negative impact of these factors on tumor behavior can be rather defined as “defifferentiation” or “anaplasia” in these tumors. The NF-kB and TGF-b pathways have been described to influence the prognosis in several types of STS, including malignant fibrous histiocytoma, Ewing sarcoma, osteosarcoma and rhabdomyosarcoma. Nevertheless, there are no reports with emphasis on the prognostic value of E-cadherin, fascin, Par-6 and PKC-f in STS. Vimentin, which is by definition expressed by all STS, is a classic marker of higher aggressivity in carcinoma. The intensity of vimentin expression can fluctuate, and the significance of this variation for the STS patients’ survival is not clear. In this study, we investigate the expression of a panel of seven molecular biomarkers in 249 non-GIST STS patients. We realize that these tumors belong to different histological subtypes and consequently have diverse prognoses. However, they all have mesenchymal derivation and belong therefore to the same generic group, STS. The investigated dedifferentiation markers reflect universal and basic processes in tumorigenesis, they are described in a variety of epithelial and non-epithelial tumors of different locations and histological entities and seem to not depend on tumor type. This is confirmed by the fact that almost each of STS type we investigated can show broad spectrum of malignancy grade, from almost benign to high grade malignant tumor. To our knowledge this is the first evaluation of such large collection of dedifferentiation-associated biomarkers in non-GIST STSs related to DSS. In our large-scale retrospective study we sought to investigate the prognostic impact of a set of biomarkers in non-GIST STS patients. These markers are known to participate in the process of EMT in epithelial tumors, but bear other important biological functions as well. Moreover, the EMT concept has not received general acceptance. STSs are of mesenchymal origin and can demonstrate a range of behavior patterns, varying from almost benign to highly aggressive tumors.