Ewing sarcoma family tumors are aggressive sarcomas of childhood and adolescence with continuing poor outcomes. Decades of research on the characteristics of the often solitary-known oncogenic-genomic aberration in Ewing sarcoma family tumors, namely a TET-ETS fusion, have provided little advancement in the understanding of the molecular pathogenesis of Ewing sarcoma or treatment thereof. In this study, the high-resolution single-nucleotide polymorphism technology was used to identify additional/secondary copy-number alterations (CNAs) in Ewing sarcoma that might elucidate the aggressive biology of this sarcoma. We compared paired constitutional and tumor DNA samples. Commonly known genomic alterations including gain of 1q and chromosome 8 were the most frequently detected changes in this study. In addition, deletions and loss of heterozygosity were identified in 10q, 11p, and 17p. Furthermore, tumor-specific CNAs were identified not only in genes previously known to be of interest, including CDKN2A, but also in genes not previously associated with Ewing sarcoma, including SOX6 and PTEN. Selected array-based findings were confirmed by fluorescence in situ hybridization, immunohistochemical studies, or sequencing. The results highlight an unexpected level of cytogenetic complexity associated with several of the samples, 2 of which contained TP53 mutations. In summary, our high-resolution genome-wide copy-number data identify several novel CNAs associated with Ewing sarcoma, which are promising targets for novel therapeutic strategies in this aggressive sarcoma.