Ubiquitination plays a key role in regulating multiple oncoproteins, including those of the Myc-family. A recent Cell paper by Adhikary et al reports that a novel E3 ligase, HectH9, mediates site-specific ubiquitination of Myc and thereby fosters a switch from repression to transcriptional activation. This insight elucidates Myc's diverse properties and provides new targets for the development of anti-cancer therapy.