The practice of clinical oncology historically has been rooted in therapy for established cancers, and over the past decade, early detection of the malignancy has occurred increasingly, allowing an increasing chance of cure by surgical intervention. Cancer prevention has been targeted largely to generic reduction of exposure to environmental carcinogens, such as smoking reduction. However, targeted identification of patients at increased risk and therapeutic tailored intervention in those patients have not taken hold in oncology, despite the enormous success of that approach in preventive cardiology. A paradigm of such a strategy for oncology may be the identification of patients with epigenetic alterations in progenitor cells and intervention before the development of the earliest identifiable neoplasms. We review studies of loss of imprinting of insulin-like growth factor 2 in colorectal cancer as an example of such a target for preventive oncology.