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The future of personalized oncological therapy will likely rely on evidence-based medicine to integrate all of the available evidence to delineate the most efficacious treatment option for the patient. To undertake evidence-based medicine through use of targeted therapy regimens, identification of the specific underlying causative mutation(s) driving growth and progression of a patient's tumor is imperative. Although molecular subtyping is important for planning and treatment, intraclonal genetic diversity has been recently highlighted as having significant implications for biopsy-based prognosis. Overall, delineation of the clonal architecture of a patient's cancer and how this will impact on the selection of the most efficacious therapy remain a topic of intense interest.