Synovial sarcoma occurs predominantly in the paraarticular regions of the extremities. Synovial sarcoma of the mediastinum is an exceedingly rare neoplasm that has overlapping histologic and immunophenotypic features with other tumors in the differential diagnosis. We describe two cases. One is a 67-year-old patient who presented with chest pain and shortness of breath. Diagnostic imaging revealed a mediastinal mass extending over the cardiac apex. Histopathology, immunohistochemistry, and molecular genetic analysis confirmed the diagnosis of synovial sarcoma. The patient underwent surgical resection and postoperative radiation therapy. He is alive and well 18 months after diagnosis. This case illustrates the importance of proper procurement of frozen tissue for molecular genetic analysis for the identification of the t(X;18), characteristic of synovial sarcoma. Detection of this translocation is of paramount importance to confirm this diagnosis, particularly when this neoplasm arises in atypical locations outside the extremities.