Recent findings on the molecular background of synovial sarcoma with the description of the specific translocation t(X;18) led to the incorporation of this particular genetic aberration into the definition of this tumor type. Synovial sarcomas with proven diagnostic translocation are being described with increasing frequency in unsuspected locations not related to joints, such as lung, pleura, heart, or pharynx. The gastrointestinal tract has been rarely reported as a primary site of synovial sarcomas with rare cases in the esophagus and stomach. We report a case of a primary synovial sarcoma of the distal duodenum with SYT/SSX2 type of the t(X;18) translocation. Primary spindle cell neoplasms of the duodenum are rare and consist mostly of gastrointestinal stromal tumors, which are amenable to the therapy with Gleevec. Synovial sarcoma widens the differential diagnosis of mesenchymal tumors of the intestine.