The formation of a high-ploidy is rare in Ewing tumor (ET) and is in contrast to some other childhood tumors such as neuroblastoma. In a series of 37 Ewing tumors analyzed by conventional cytogenetics, 4 of the 34 tumors with an abnormal clone (11.8%) demonstrated the presence of a high-ploidy clone, with a chromosome number that ranged from hypotriploid to pentaploid. All 4 contained a t(11;22)(q24;q12) and the karyotypes had further aberrations of the type that would be generally expected in ET. Numerical aberrations represented the majority of the karyotypic events identified and gain of chromosome 8 and loss of chromosomes 3, 10, 16, 19, and 22 occurred in at least 3 tumors. However, no single mechanism could be implicated to explain the karyotypic picture of the 4 cases. It is proposed that high-ploidy subgroups exist in ET and it would be potentially erroneous to group these and other cases together when determining their clinical implications.