In head and neck squamous cell carcinomas (HNSCC) the prognostic factors that are routinely considered when deciding therapeutic strategies are still stage and site of the primary tumour, and the presence of nodal or distant metastases. However, it is recognised that these clinical predictors are limited since they do not satisfactorily reflect the biological behaviour of the individual tumour. With the evolving understanding of the genetic and molecular basis of human malignancies, there are an increasing number of factors being claimed to provide prognostic information even in HNSCC. Here we review own and published data on DNA ploidy, karyotyping and molecular cytogenetic changes and its relevance in HNSCC carcinogenesis. The survey suggests that the induction of aneuploidy is a very early event in tumour development being detectable already in non-dysplastic leukoplakia and highly predictive for the subsequent development of a carcinoma. Moreover, specific chromosomal imbalances are associated with different stages of cancer progression and patient's survival, which we have compiled into a progression model of HNSCC.