Mutations in the p53 tumour suppressor gene and amplification of the cyclin D1 (CCND1) oncogene have been commonly reported in various malignancies. In the present study of 39 squamous cell carcinomas of the head and neck, p53 mutations were manifest in 11 (28%) of the cases, whereas CCND1 amplification was seen in 6 (16%) of 37 analysed tumours. The 10 mutations occurring in coding sequences of p53 were found in exon 5 (4 cases), exon 6 (3 cases),f and exon 8 (3 cases). No mutation was found in exon 7. Eight of the 10 exon nucleotide substitutions were missense mutations and two were nonsense mutations. All six tumours with CCND1 amplification also had p53 mutations, while an additional five tumours manifested p53 mutations in the absence of CCND1 amplification. There was a statistically significant positive correlation between these two gene alterations. This raises the possibility that mutation of p53 precedes CCND1 amplification in carcinogenesis.