Antibodies against the p53 protein are produced by some cancer patients. In some tumour entities, the presence of p53 autoantibodies have been linked to poorer survival. This study was designed to assess the prevalence and prognostic implications of p53 autoantibodies in patients with lung cancer. Serum samples of 180 patients were tested for antibodies against p53 protein using an ELISA. We studied 134 patients with primary lung cancer [histology: small cell lung carcinoma (SCLC) n=35; non-small cell lung carcinoma (NSCLC) n=99]. The control group consisted of 46 patients without lung cancer. In 17/134 (12.6%) of the cancer patients, p53 autoantibodies were detected (4/35 SCLC, 13/99 NSCLC). Most of the positive results were found in advanced stages of NSCLC (stage I-IIIA: 1/34; stage IIIB/IV: 12/65). One of the 46 control patients tested positive. Statistical analysis of survival shows no correlation with p53 antibody status in SCLC, but a significant correlation with shorter survival in NSCLC (p=0.01). After correction for stage of disease this correlation remains significant (stage IIIB/IV: p=0.02). In our series, the presence of anti-p53 autoantibodies is almost exclusively linked to the presence of malignant disease. Prognosis for patients with NSCLC, but not SCLC seems to be linked to the p53 autoantibody status.