Granulocytic sarcoma (GS) is a rare manifestation of acute myeloid leukemia (AML), blastic transformation of chronic myeloid leukemia, and the myelodysplastic syndromes. The mediastinum is an unusual site of presentation. We report a series of three female patients with mediastinal GS. They were characterized by the presence of large and bizarre blast cells and near tetraploidy on cytogenetic analysis. All three patients responded poorly to chemotherapy. Near tetraploid AML is a rare entity, usually present in male patients, and has not been associated with GS. The clinical and pathological similarities in these three cases suggest a distinct category of poor-risk AML for which more intensive treatment is needed.