Taken together, our results reveal that TGF-β signalling inhibition, whether achieved by MYCN overexpression or pharmacological treatment, strongly contributes to resistance to retinoid-mediated differentiation in neuroblastoma cells and that pharmacological activation of TGF-β signalling represents a promising strategy to sensitising MYCN-amplified cells to retinoid-mediated apoptosis. This evidence concerns the gene TGFB1 and neuroblastoma.