Tissue samples from 60 post-Chernobyl childhood thyroid tumors have been investigated. We used comparative genomic hybridization (CGH) to detect chromosomal gains and losses within the tumor DNA. This is the first CGH study on childhood thyroid tumors. The post-Chernobyl tumors showed chromosomal imbalances in 30% of tumors. The most frequent DNA copy number changes in post-Chernobyl tumors involved chromosomes 2, 7q11.2-21, 13q21-22, 21 (DNA gains), and chromosomes 16p/q, 20q, 22q (DNA losses). Some of these specific alterations detected in post-Chernobyl thyroid tumors (deletions on chromosomes 16p/q and 22q) have previously been reported in thyroid tumors as associated with an aggressive biologic behavior and may therefore also account for the more aggressive phenotype of papillary thyroid carcinoma (PTC) found in post- Chernobyl tumors. Eighteen percent of post-Chernobyl PTC that exhibit RET rearrangements also showed chromosomal imbalances indicating that either additional genetic events are involved in this subset of tumors, or that intratumoral genetic heterogeneity exists in these tumors, suggesting a oligoclonal pattern to tumor development.