Oncogenesis and tumour progression are caused by the progressive accumulation of genetic and epigenetic abnormalities in pre-cancerous and cancerous cells, conferring increased capabilities of proliferation and survival. Recent technological advances, including the development of CGH arrays and high-throughput sequencing, have made it possible to map the genetic landscape of human cancers. Molecular characterisation studies have provided key insights into the disease mechanisms that can be used for the design of tailored therapies and have led to the identification of specific biomarkers for guiding patient management. Nevertheless, the genetic instability of cancer cells and the consecutive intra-tumoral heterogeneity remain critical constraints in the context of the emergence of targeted therapies.