The expression of H-ras, K-ras and N-ras oncogenes was analyzed on frozen sections of squamous cell carcinoma of the head and neck (SCCHN) by immunohistochemistry using anti-ras monoclonal antibodies. Of 22 primary SCCHN, 15 (68%) stained positive for H-ras, 10 (45%) for K-ras and seven (32%) for N-ras. Thirteen specimens (59%) stained positive for at least two anti-ras monoclonal antibodies. The presence of immunohistochemically detectable H-ras, K-ras and N-ras proteins was most frequently associated with an increase in tumor size and later stages of disease (T3 and T4), with no apparent correlation with lymph node involvement, site of occurrence, degree of differentiation, age, sex, or race. Thus, overexpression of members of the ras gene family occurs as a relatively common even in SCCHN and may be an important event in the later stages of tumorigenesis.