Neuroendocrine and neuroectodermal tumors are interrelated, and comprise a neoplastic family including lesions formerly termed "carcinoid," "atypical carcinoid," "small cell undifferentiated carcinoma," "primitive neuroepithelioma," "chemodectoma," and "neuroblastoma," to name but a few entities. The nosology of these neoplasms has been simplified recently, in part as a result of a better understanding of their immunophenotypes and molecular biological attributes. This review considers those immunohistochemical markers that are now generally available for diagnostic evaluation of neuroendocrine and neuroectodermal differentiation, and provides information on the relative sensitivity and specificity of each of them. Intermediate filament proteins, chromogranins, synaptophysin, CD56, CD57, CD99, neuron-specific (gamma-dimer) enolase, protein gene product 9.5, and specific neuropeptide products are discussed. The application of such determinants in regional differential diagnosis is also summarized.