Traditional diagnostic methods such as clinical assessment, histopathological examination and imaging techniques are limited in their capacity to provide information on prognosis and treatment choice of head and neck cancer. In recent years, molecular techniques have been developed that enabled us to get more insight into the molecular biological cellular pathways underlying tumor progression and metastasis. Correlation of these molecular changes with clinical events has been explored. However, consistently useful markers have not been identified yet, although many promising developments are in progress. It may be expected that in the near future, molecular markers will be useful for clinical purposes. In this paper, an overview will be given of the several molecular techniques that may have potential to be introduced in clinical practice in the management of head and neck squamous cell carcinoma.