Primary mediastinal endodermal sinus tumor is rare, and to date only 49 cases have been described in the English-language literature. Seven new cases are reported. Light microscopic examination showed characteristic features including papillary, reticular, tubular and solid growth patterns, complete or incomplete Schiller-Duval bodies and intracellular or extracellular periodic acid-Schiff-positive material. Immunohistochemical studies showed alpha-1-antitrypsin in seven, alpha-fetoprotein in seven, keratin in six, and carcinoembryonic antigen in four cases. The beta subunit of human chorionic gonadotropin, albumin, fibronectin, and transferrin were not found in any case. Electron microscopic studies performed in four cases showed intracellular and extracellular basement membrane-like material, multiple large multivesicular bodies, desmosomes and microvilli. Mediastinal endodermal sinus tumor can and must be differentiated from poorly differentiated adenocarcinoma metastatic or extending to the mediastinum because of the distinctly different prognoses and therapies. In spite of modern chemotherapy, the prognosis of mediastinal endodermal sinus tumor remains poor. The single most important prognostic indicator is whether the tumor mass can be completely excised before or after chemotherapy.