Squamous cell carcinoma of the pharynx and larynx (SCCPL) is a genetically complex disease and is frequently associated with nonrandom chromosomal alterations. Fifty primary SCC of the pharynx (oropharynx, n=11): see and hypopharynx, n=11) and larynx ( n=28) were examined for numerical aberrations of chromosomes 8, 9, 11, and 17 with a panel of chromosome-specific repetitive DNA probes by fluorescence in situ hybridization (FISH). DNA ploidy analysis was also performed by flow cytometry (FCM). Aneusomic copy numbers of chromosomes 8, 9, 11, and 17 were discovered in 66%, 68%, 68% and 78% of tumors, respectively. FCM showed abnormal DNA content in 74% of cases (mean DNA index=1.69). Polysomy was the main finding in both DNA-aneuploid and DNA-diploid tumors (64.5% of cases). Numerical aberrations of chromosomes 8 and 11 correlated to DNA ploidy by FCM (P< 0.05). Aneusomy was present in 69.23% of DNA-diploid tumors. Marked intratumoral and intertumoral chromosomal heterogeneity was noted between individual tumors, suggesting a notable heterogeneity in aneuploid and diploid cell populations. Interphase FISH can be used to study important cytogenetic changes which occur during the development of SCC of the pharynx and larynx.