Neoplasms of APUD cell origin are quite variable in their metastatic behavior. Whereas pituitary and parathyroid tumors almost never metastasize, all oat cell lung cancers, malignant melanomas, trabecular carcinomas of the skin and medullary thyroid cancers are capable of dissemination. The metastatic proclivity of individual carcinoids, pancreatic and extrapancreatic islet cell tumors, and paragangliomas is much less predictable. In particular, there are no reliable histological markers of risk for lymphatic or hematogenous dissemination. The behavior of many carcinoids, islet cell carcinomas and paragangliomas is relatively indolent, even when metastatic disease is already present. However, unresectable distant metastases, especially liver involvement, connote a poor prognosis. Mortality is more often related to uncontrolled tumor growth and metastasis than to associated endocrinopathies. Curative or debulking surgical resection should be aggressively pursued as recent data show that worthwhile clinical disease-free survival can be realized in at least some patients.