Several morphological methods are currently available for the demonstration of neuroendocrine differentiation. Silver impregnation techniques to show argyrophilia or argentaffinity are reliable albeit limited tests for neuroendocrine cells. Immunocytochemistry, at the light or electron microscopic level, is now a routine technique in many histopathological departments. General neuroendocrine markers can be immunostained to define the nature of a tumour or, using antisera to specific neuroendocrine cell products, the exact type of tumour can be established. The application of a range of antisera to bioactive peptides and other derivatives of their precursors can increase the efficiency of detection and classification of neuroendocrine tumours. The latest technology available goes beyond looking at neuroendocrine cell products and investigates peptide gene expression. In situ hybridisation of DNA or mRNA species thereby adds a new dimension to the morphological analysis of neuroendocrine tumours. Used in combination with immunocytochemistry, this technique can provide information on intracellular hormone synthesis. The study of markers of neuroendocrine differentiation continues to yield information which aids not only the diagnosis of neuroendocrine tumours but also the understanding of their biology and the effects exerted by their products.