Since the discovery of epigenetic alterations in cancer 20 years ago by Feinberg and Vogelstein, a variety of such alterations have been found, including global hypomethylation, gene hypomethylation and hypermethylation, and loss of imprinting (LOI). LOI may precede the development of cancer and may thus serve as a common marker for risk, but also as a model for understanding the developmental mechanism for normal imprinting.