Background: The prognostic divergence of laryngeal and hypopharyngeal carcinomas is well known. Hypopharyngeal tumors are characterized by frequent metastasis formation and local recurrence, which is the source of the unfavorable prognosis of this subtype. The aim of this study was to define chromosomal alterations associated with the aggressive behavior of hypopharyngeal tumors. Methods: Twenty-nine head and neck squamous cell carcinomas (larynx n 5 14 and hypopharynx n 5 15) were analyzed by comparative genomic hybridization (CGH). Fluorescence in situ hybridization (FISH) was used to validate the CGH data and to compare the amplification pattern of the most frequently altered gene (cyclin-D1, CCND1) located on 11q13. Results: The average number of genetic alterations was significantly higher in the hypopharyngeal tumors (P 5 0.02). A good correlation of FISH and CGH data were