Synovial sarcoma (SS), a translocation-associated sarcoma characterized by SS18-SSX1/2 fusion, presents most often in the extremities of young adults. While SS regularly occurs in the pleuropulmonary parenchyma, the mediastinum is an exceedingly rare primary site; the literature on this subject is predominantly composed of case reports and small series, mostly without molecular confirmation. Cases of mediastinal SS were selected from our institutional and consultation archives. Diagnoses were confirmed by either SS18 fluorescence in situ hybridization (n=6) or reverse transcription polymerase chain reaction for SS18-SSX1/2 (n=15). Mediastinal SSs occurred in 21 patients (15 men; mean age, 38 y; range, 21 to 75). Only 1 patient was older than 50 years. Average tumor size was 13.5 cm (range: 6.4 to 23 cm). One tumor was biphasic and the rest were monophasic, 11 of which were poorly differentiated (52%). Of 10 cases with known fusion transcripts, 6 had SS18-SSX2 and 4 had SS18-SSX1. Follow-up was known for 16 patients (mean: 18.9 mo; range: 5 to 45): 14 had local disease progression or recurrence, and 6 had metastasis. Death from disease occurred in 11 of 16 patients (69%) at 5 to 32 months, and 5 (36%) were alive with disease at last follow-up (6 to 45 mo). Mediastinal SS is a rare and aggressive malignancy most common in patients younger than 50 years. Most are monophasic and reach large size before detection. Poorly differentiated morphology is common. SS should be included in the differential diagnosis of spindle cell, biphasic and poorly differentiated mediastinal tumors. Because of the rarity of SS at this site, molecular testing is recommended to confirm the diagnosis.