Large-scale, genomic studies of specific tumors such as The Cancer Genome Atlas (TCGA) have provided a better understanding of the alterations of pathways involved in the development of solid tumors including glioblastoma, breast cancer, ovarian and endometrial cancers, colon cancer and lung squamous cell carcinoma. This tremendous effort of the scientific community has confirmed the view that Cancer actually represents a wide variety of diseases originating from different organs. These studies showed that TP53 and PI3KCA are the two most mutated genes in all types of cancers and that 30% to 70% of all solid tumors harbor potentially 'actionable' mutations that can be exploited for patient stratification or treatment optimization. Translation of this huge oncogenomic dataset to clinical application in personalized medicine programs is now the main challenge for the future. The gap between our basic knowledge and clinical application is still wide. Closing the gap will require translational personalized trials, which may initiate a radical change in our routine clinical practice in oncology.