Objective: Synovial sarcomas are mesenchymal tumors of unknown histogenesis. Their molecular signature is a specific t(X; 18)(p11.2;q11.2) translocation. No effective targeted therapies are currently available. The aim of this study was to evaluate the expression and mutational status of potential molecular therapeutic targets. Method: 38 molecularly confirmed cases of synovial sarcomas were included in this study. Immunohistochemical stainings of the EGF-R family (EGF-R, HER2/neu, HER3), and signaling molecules implicated in the mTOR pathway (AKT, mTOR, PTEN), as well as E-Cadherin and snail was performed. In addition, cases were screend for mutations in the EGFR, PIK3C, B-RAF, K-RAS, and N-RAS genes. Results: EGF-receptor family members as well as E-Cadherin and snail are important for defining the tumor phenotype by determining epithelial-mesenchymal transition of synovial sarcomas. Activation oft the mTOR pathway is seen in a significant number of cases. Mutations of the genes studied are an overall rare event in synovial sarcomas and other types of sarcomas studied. Conclusion: EGF-R expression is found in many synovial sarcomas, however, mutations of EGFR or downstream molecules appear to be rare. Activation of mTOR pathway is frequently seen in synovial sarcomas. The benefit of targeted therapy against these genes in synovial sarcomas remains to be determined.