p53 autoantibodies (AAB) are a new serological parameter with unknown potential in patients with malignancies. The reason why and the mechanism by which they develop is still unclear. So far, only in a limited number of studies has the usefulness of p53 AAB in the follow-up of cancer patients been shown. In this study 32 patients with head and neck cancer, seropositive for p53 AAB in their serum detected with an ELISA, were followed-up for at least 42 months. In 9 out of 32 p53 seropositive AAB head and neck cancer patients a correlation with the clinical course of the disease was seen. The remaining 23 of the p53 AAB-positive patients did not demonstrate any significant AAB titer changes during the follow-up and no significant correlation with the clinical course was observed. In conclusion, the clinical value of p53 AAB as a tumor marker for patients with head and neck cancer seems to be limited.