Secretagogin (SCGN) is a novel calcium-binding protein which consists of six EF-hand domains. This protein was first identified as a pancreatic β-cell specific calcium-binding protein. SCGN has been detected in neuroendocrine cells of the pancreas and GI tract. In the central nervous system, SCGN was detected in a neuron-specific expression pattern with high expression in basket and stellate cells of the cerebellar cortex, in secretory neurons of the anterior region of the pituitary gland and in singular neurons of the frontal and parietal neocortex. Remarkable staining intensity was observed in hypothalamic and in hippocampal neurons. Co-localization of SCGN with other neuroendocrine markers (chromogranin A, neuron-specific enolase and synaptophysin) has been observed in neuroendocrine cells of normal mucosa. SCGN can be used to detect small cell lung cancers. Compared to chromogranin A, SCGN is more sensitive in the identification of a subset of neuroendocrine tumors, such as gastric neuroendocrine cancers and typical carcinoid tumors of rectum and ovary. SCGN is a useful marker for neuroendocrine differentiation.