Abstract In the present study, we analysed p53 autoantibodies from patients with head and neck cancer by ELISA, by Western blot using C- and N-terminal fragments of p53 and with peptide libraries of p53. We found that 8.2% of the patients with head and neck cancer developed antibodies against p53. Using additional p53 autoantibody-positive sera from patients with head and neck cancer, we found that all of these sera recognised common epitopes, which were also recognised by well-known mouse monoclonal antibodies against p53. Common epitopes are located in regions on the polypeptide chain of p53, which are functionally important for the role of p53 in growth control. Thus, the knowledge of these epitopes might be useful for the development of new strategies for cancer therapy.