Soft tissue sarcomas are a highly heterogenous group of malignant tumors that originate from mesenchymal tissues including muscle, adipose and fibrous tissues, blood vessels, and peripheral nerves. A large variety of histological subtypes that current diagnostic approaches recognize present a diagnostic challenge because their clinical and histopathological characteristics are not always distinct. One of the important clinical problems is a lack of useful biomarkers; therefore, the discovery of biomarkers that can be used to detect tumors or predict tumor response to chemotherapy or radiotherapy could help clinicians provide more effective clinical management. Recent reports on microRNAs (miRNAs) in soft tissue sarcomas have provided clues to solve the problem. Evidence for miRNAs in tumor tissues as well as circulating miRNAs in patients’ blood is accelerating the potential to transform clinical applications. In this chapter, we summarize the emerging evidence of dysregulated miRNAs in tumor tissues and patients’ blood and discuss the potential of miRNAs as novel biomarkers and therapeutic targets.