MYC in human epidermal stem cells can stimulate differentiation rather than uncontrolled proliferation. This discovery was, understandably, greeted with scepticism by researchers. However, subsequent studies have confirmed that MYC can stimulate epidermal stem cells to differentiate and have shed light on the underlying mechanisms. Two concepts that are relevant to cancer have emerged: first, MYC regulates similar genes in different cell types, but the biological consequences are context-dependent; and second, MYC activation is not a simple 'on/off' switch — the cellular response depends on the strength and duration of MYC activity, which in turn is affected by the many cofactors and regulatory pathways with which MYC interacts.