Using this gene selection and validation approach, we identified eight efficient transcriptional markers to predict the presence of HNSCC cells in tissue samples, with three remarkable markers: IL1RN, MAL and MMP1. When tested individually, these three markers presented specificity above 91% and sensitivity above 93% in a cohort of 46 patients with various stages, grades and sites of the disease. This evidence concerns the gene MMP1 and head and neck squamous cell carcinoma.