The p53 codon 72 polymorphism, resulting in either an arginine or a proline residue has been proposed to affect the susceptibility of p53 protein to human papilloma virus (HPV) E6-mediated degradation in vitro. However, there are controversial results from several clinical studies in various human tumours. The purpose of our study was to investigate the significance of this p53 genotype with respect to the risk of neoplasia development in Greek patients with benign and malignant laryngeal tumours. Furthermore, we searched for an association between p53 alleles and the presence of HPV in the same series of samples. We found a significant statistical association in the distribution of p53 genotypes between laryngeal lesions and normal samples (P<0.001). Allelic analysis of the patients with both benign and malignant tumours revealed a striking over-representation of the homozygous p53Arg allele compared to normal population (P<0.0003). HPV was detected in only 3 laryngeal samples (1 benign and 2 malignant tumours). This is the first study correlating the p53 codon 72 polymorphism in laryngeal tumours. Our results provide evidence that this p53 polymorphism may be implicated at the early stages of the disease and concerns predisposition to premalignant laryngeal lesions rather than to progression from benign tumour toward malignancy. Moreover, we demonstrate that the p53Arg homozygous genotype affects the predisposition for laryngeal tumours while the heterozygous status does not. The low incidence of HPV infection suggests that it is not a major oncogenic factor in the development of laryngeal tumours but may have synergistic action with specific genotypes of p53 gene.