This study reports a case of papillary carcinoma with vesicular components showing multiclonal aberrations of chromosome 22 as revealed by RHG-banding cytogenetics and by fluorescence in situ hybridization (FISH; whole chromosome 22 and BCR-ABL-specific locus probes, multi-FISH). Four clones with chromosome 22 changes as the sole abnormality were seen. The main abnormal clone lacked the whole chromosome 22. A del(22)(q11) was observed in a second group of cells. The third clone had an idic(22). Finally, FISH revealed a fourth abnormal cell population with a der(17)t(?17;22). Some of these chromosome 22 alterations have been described in other solid tumors such as meningiomas and neurinomas, suggesting a common genetic pathway of tumor progression occurring in a multistep process. Chromosome 22 changes do not seem to be involved in pure papillary thyroid tumors and therefore could be related to the maintenance of a follicular-type histological pattern.