Mediastinal germ cell tumors are among the most common tumors in the anterior mediastinum. This tumor should be considered strongly in the differential diagnosis of anterior mediastinal masses. Benign teratomas are common in this site, and complete surgical resection results in cure of nearly all patients. Malignant mediastinal seminomas are highly curable and either radiotherapy (mediastinal disease) or cisplatin-based chemotherapy (metastatic disease) will result in long-term survival in 80% or more of patients. Mediastinal nonseminomatous germ cell malignancies represent a clinically and biologically distinct subset of mediastinal germ cell neoplasms. Relative to their testicular counterparts, these tumors carry a poor prognosis, but, with newer refinements in cisplatin-based chemotherapy, approximately half of these patients will survive their illness. The history of success with chemotherapy should prompt thorough pathologic and serologic evaluation of all patients with mediastinal malignancies in hopes of defining a curable process. In particular, poorly differentiated carcinomas at this site should be treated as germ cell tumors, and so long-term survival will be attainable. Mediastinal nonseminomatous germ cell tumors are associated with the development of nongerm cell malignancies such as embryonal rhabdomyosarcomas and hematologic malignancies such as acute megakaryocytic leukemia and malignant histiocytosis. The development of these associated malignancies is not related to therapy and represents a true biological link between these malignancies. It is likely that the development of these malignancies is an expression of the multipotential nature of primitive germ cells. Careful clinical and biologic investigations of these rare transformations may lead to greater understanding of the regulation of events in the malignant process.