Epigenetic states generate high-fidelity cellular memories that orchestrate normal development. Conversely, epigenetic lesions, or epigenetic amnesia, are common features in human cancer documenting the frequent appearance of low-fidelity epigenetic states during neoplasia. The chromatin insulator protein CTCF emerges as a central player, since it interacts with all known vertebrate chromatin insulators and is perceived to partition epigenetically controlled expression domains. Moreover, it may shape epigenetic states by both interpreting epigenetic marks and maintaining methylation privilege regions. We will present recent results which impinge on the dual role of CTCF and its sibling, BORIS, in establishing and interpreting gametic imprints and the dysregulation of these features in cancer.