Nitric oxide (NO) is a negative regulator of proliferation in many cell types, including neural cell precursors, in which it promotes neuronal differentiation. By contrast, the protooncoprotein N-Myc promotes proliferation of neuronal precursors and is downregulated in neuroblastoma cells induced to differentiate by retinoic acid. This prompted Elisabetta Ciani and colleagues to ask whether the antiproliferative action of NO in neuronal precursors is mediated by negative regulation of N-Myc expression(see p. 4727). They show that increasing NO levels in retinoic-acid-treated neuroblastoma cells, by overexpressing neuronal NO synthase (nNOS) or exposing the cells to an exogenous NO source, slows down their proliferation, accelerates their differentiation, and decreases N-Myc expression. Conversely, nNOS inhibition in cerebellar granule cell cultures increases both neuronal precursor proliferation and N-Myc expression. The authors conclude that NO regulates a switch in neuronal precursor programming, from proliferation to differentiation, through N-Myc and suggest that this new function for NO could provide a therapeutic target for the treatment of aggressive N-Myc-expressing neuroblastomas.