Relatively few variant translocations have been reported in primary Ewing's sarcomas (ES). We report two new variant translocations, both of which involve chromosomal rearrangements of 22q12. Cytogenetic studies of tumor cells from a 12-year-old girl revealed a variant translocation, t(7;22)(p22;q12), the second example reported of a simple variant of the 22q12 reciprocal translocation in this type of sarcoma. The identity of this rearrangement was confirmed by in situ hybridization. In addition, a complex translocation was identified in a dysmorphic 15-year-old girl, t(4;11;22)(q21;q24;q12). No previous cases of variant translocations in ES have involved band 7p22 or 4q21, and there are no previous reports of an association between congenital abnormalities and unusual karyotype abnormalities in ES. Both variant translocations conserve the junction on the der (22), providing additional cytogenetic evidence that the sequences on chromosome 22 are critical.