The new high-throughput “omics” technologies have recently opened the possibility to identify molecular changes and metabolic pathways in each cancer type with the possibility of molecular tumor subclassification and identification of a more reliable prognosis and appropriate treatment [1–3]. A further result is the reduction of overtreatment of those with higher responsivity and better prognosis. Furthermore, such studies do have the possibility of identifying specific cancer targets, with higher effectiveness of chemotherapy and much lower general toxicity. The whole field is in a current turmoil, and this specific issue, focused on the clinical validation of newly identified biomarkers, has been able to bridge molecular mechanisms with clinical diagnosis and therapeutic responsivity touching different aspects of this topic. The two major topics have been (a) characterization of biomarkers for more specific cancer diagnosis and prognosis; (b) identification of biomarkers for progression evaluation and therapeutic responsivity. Biomarkers of cancer susceptibility have been also reported.