Abstract SK‐N‐SH and SH‐SYSY human neuroblastoma cells treated by 12‐ O ‐tetradecanoyl‐phorbol‐13‐acetate (TPA) express morphological and biochemical changes, which indicate that differentiation towards more mature cells has occurred. The most prominent morphological changes were the development in 40–60% of the cells of cell‐surface projections longer than 50 μm and cytoplasmic neurosecretory granules demonstrated by electron microscopy. At the biochemical level, TPA induced a two‐fold increase in the relative activity of neuron‐specific enolase and 30‐ to 40‐fold increase in noradrenaline and adrenaline concentrations. A decrease in proliferation rate of TPA‐treated cells was observed. The biological effects of TPA were slightly potentiated by nerve growth factor.