The generation of dense-core granules (DCGs), exocytic organelles present in neurones and neurosecretory cells, is thought to be controlled by coordinate gene expression programmes specific to these cell types. However, recent studies have suggested that expression of a single cargo protein - chromogranin A (CgA) - can drive DCG formation both in neurosecretory and in non-neurosecretory cells. On p. 743, Jacopo Meldolesi and co-workers resolve this controversial issue by showing that the ratio between CgA and its secretory protein mate chromogranin B is randomly variable between clones isolated from the heterogeneous PC12 neurosecretory cell line, between cells within clones, and between granules in single cells. Increased expression of CgA (by stable or transient transfection) did not increase the number of granules in a PC12 clone containing few DCGs nor did it induce DCG formation in three non-neurosecretory cell lines; instead in non-secretory cells it induced the formation of CgA-containing lysosomes. The authors conclude that a CgA-dependent on/off switch is not involved in DCG expression and that DCGs are true hallmarks of neurosecretory cells.