The serum level of a variety of substances shows significant changes in head and neck cancer patients. Such substances are collectively called biochemical tumor markers. To date, most markers lack a high degree of specificity and sensitivity. However, serial measurement of markers showing elevated pretreatment levels may help in monitoring response to therapy. Other potential uses of tumor markers include earlier detection of recurrence and/or metastasis, and possible prediction of prognosis. Measurement of more than one marker seems to enhance the diagnostic accuracy of the test. Some markers show significant correlations with various immune parameters in head and neck cancer patients and may have a possible role in potentiating the immunodepressed status of such patients. A review of currently reported tumor markers in head and neck cancer showing their nature, sources, uses, and limitations is presented.