The systematic classification of malignant disease creates a common language among the participants involved in cancer diagnosis and treatment. Classifications provide information regarding disease prognosis and the selection of treatment for patients, and may indicate when a novel treatment is required. Thus, systems of classification require revision over time as knowledge accumulates about the effects of therapy. Clinical experience over the last decade with biologically targeted anticancer agents has exposed the increasing inadequacies of many current classifications of malignant disease and the need for greater patient-specific biological characterization of cancer. Recent efforts to characterize the biology of tumors using new technologies and relate this information to clinical oncology practice are discussed in this review. The results to date reveal important biological diversity within classification groups based on histology. In addition, methods to more comprehensively analyze data on the biology of the tumors of individual patients than are currently used may make the development process of anticancer therapeutics more efficient.