Cytogenetic techniques for the analysis of genetic changes common in head and neck squamous cell carcinogenesis show complex patterns of chromosomal deletions, translocations, and amplifications. Powerful molecular biologic techniques have recently made possible the investigation of these abnormalities at the DNA level. Tumour suppressor gene loss and oncogene activation can now be recognized in tumours. Multiple genetic loci are implicated in the carcinogenesis process, while much evidence points to the existence of yet to be recognized tumour suppressor genes. An overview of the genetic changes commonly seen in head and neck squamous cell carcinogenesis and the possible implications of these are presented.