Cancer is a multifaceted disease that involves acquisition of genetic mutations, deletions, and amplifications as well as deregulation of epigenetic mechanisms that fine-tune gene regulation. Key epigenetic mechanisms that include histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing are often deregulated in a variety of cancers. Subnuclear localization of key proteins in the interphase nucleus and bookmarking of genes by lineage commitment factors in mitosis—a new dimension to epigenetic control of fundamental biological processes—is also modified in cancer. In this review, we discuss the various aspects of epigenetic control that are operative in a variety of cancers and their potential for risk assessment, early detection, targeted therapy, and personalized medicine. J. Cell. Physiol. 228: 2103–2108, 2013. © 2013 Wiley Periodicals, Inc.