This study sought to analyze the influence of the microenvironment upon the behavior of HNSCC.Study Design: The status of pAkt, NF-κB and Cyclin D1 proteins was accessed through immunofluorescence and western blot methods in HNSCC cell lines originating from tongue, pharynx and metastatic lymph node when submitted to a three-dimensional culture model utilizing a matrix system. Here, CCND1 is linked to head and neck squamous cell carcinoma.