Internationally accepted classifications of malignant tumors, developed by the World Health Organization (WHO) and the Union for International Cancer Control (UICC), are based on the histotype, site of origin, morphologic grade, and spread of cancer throughout the body. The WHO classifications are the foundation of cancer diagnosis and the starting point for cancer management. Starting in 2000, the WHO classifications began to include biologic and molecular-genetic features. These developments are having a strong impact on cancer diagnosis and treatment, and this impact is amplifying, given the advances in cancer genomics. Molecular-genetic profiling can be used to refine existing classifications of tumors and, for a small but increasing number of cancers, even determine the treatment irrespective of histotype. Here I discuss how cancer classifications may change in the era of cancer genomics.