Pan-genomic analyses of genetic and epigenetic alterations and gene expression profiles are providing important new insights into the pathogenesis and molecular classification of cancers. The technologies and methods used for these studies are rapidly diversifying and improving. The use of such methodologies for the analysis of adrenocortical tumours has revealed clear transcriptomic (mRNA and microRNA expression profiles), epigenomic (DNA methylation profiles) and genomic (DNA mutations and chromosomal alterations) differences between benign and malignant tumours. Interestingly, genomic studies of adrenal cancers have also identified subtypes of malignant tumours, which demonstrate distinct patterns of molecular alterations and are associated with different clinical outcomes. These discoveries have created the opportunity for classifying adrenocortical tumours on the basis of molecular analyses. Following these genomic studies, efforts to develop new molecular tools that improve diagnosis and prognostication of patients with adrenocortical tumours have also been made. This Review describes the progress that has been made towards classification of adrenocortical tumours to date based on key genomic approaches. In addition, the potential for the development and use of various molecular tools to personalize the management of patients with adrenocortical tumours is discussed.