Gene expression profiling within pathologically defined malignancy uncovers new categories of cancer classes, including head and neck squamous cell carcinomas (-HNSCC).However, the molecular signatures and transcriptional regulatory mechanisms underlying the heterogeneity in HNSCC and their responses to therapy are still elusive.Genome-wide cDNA mieroarray profiling of a panel HNSCC cell lines revealed novel gene expression signatures which distinguished cancer cell subsets associated with their p53 status.Three major clusters of genes were identified through hierarchical clustering, gene ontology and statistical modeling.