Since the discovery of somatostatin (SS) and of its interactions with a family of specific somatostatin receptors (sst), a wide body of evidence has been reported on its biological activities. Those activities include inhibition of hormone secretion, neuromodulatory properties in the central nervous system, cell growth control, and induction of apoptosis. At the same time, the distribution of sst has been analyzed in both normal and pathological tissues and sst subtype selective SS-analogs, able to mimic most SS functions, have been developed. The results have been fundamental insights into sst physiology and potent clinical implications in a variety of neoplastic and non neoplastic diseases. Neuroendocrine tumors have been particular targets of investigation. Alternative methods have been validated and are available to analyze the presence and functionality of sst at the level of either mRNA or protein. These methods include RT-PCR, Northern blot, in situ hybridization, immunohistochemistry, autoradiography, and in vivo scintigraphy. Tissue localization techniques are now accessible to many pathology laboratories worldwide and the role of the pathologist in typing the different sst present in a given sample is becoming more and more crucial. This is particularly, but not exclusively, the case in the field of neuroendocrine oncology, where sst typing may affect the clinical management of patients with sst-positive tumors.