Rare cases of adult onset acute megakaryoblastic leukemia are associated with malignant mediastinal germ cell tumor. In these cases, the mediastinal germ cell tumor develops before or concomitantly with but not after acute megakaryoblastic leukemia. The three most common genetic aberrations in the bone marrow cells of these individuals (representing ~65% of all cases) are inversions in the long arm of chromosome 12, trisomy 8, and an extra X chromosome. In several of these cases, the genetic aberrations in the malignant megakaryoblasts were similar to those in the malignant mediastinal germ cells. These results and those of other analyses suggest that the two malignancies derive from a common founding clone of cells (i.e. a set of genetically identical cells).