DNA sequencing techniques have evolved rapidly in the last 5 years by the introduction of new sequencing machines, denominated second-generation sequencers, next-generation sequencers or massive parallel sequencers. These technologies make it possible to determine the complete sequence of the human genome, or selected regions of it, at accessible prices and in a short period of time. Therefore, it is now possible to determine the nucleotide sequence of the DNA from cancer cells and to compare it to that of normal cells to identify the genetic changes involved in cancer generation. Actually, the genome of more than 15 tumour types has been determined in the last 3 years. The results obtained have allowed the identification of new cancer driving genes, new susceptibility genes and the detailed identification of genome structural reorganisations. In this review a brief description of the new sequencing technologies will be presented. Recent findings on cancer genome and exome sequencing will be summarised. Finally, the potential applications of these new technologies to cancer prognosis, diagnosis and therapeutics will be discussed.