Between September 1983 and December 1988, we observed 16 cases of hematologic neoplasia associated with mediastinal germ-cell tumors. twenty-eight similar cases have been reported in the literature. A review of the clinical and cytogenetic details in these patients suggests that the hematologic neoplasia is not the result of cisplatin-based chemotherapy of the mediastinal germ-cell cancer. This syndrome was found only in patients with nonseminomatous mediastinal germ-cell tumors, particularly those with serologic or histologic evidence of yolk-sac elements. The two most common hematologic neoplasms seen in this syndrome were acute megakaryoblastic leukemia and malignant histiocytosis. Consistent cytogenetic abnormalities have not yet been identified, but the finding of the marker chromosome isochromosome(12p) in the mediastinal germ-cell tumor and associated leukemic blasts in one patient suggests that these tumors may arise from a common progenitor cell. (N Engl J Med 1990; 322: 1425–9.).