Patients with rare tumors represent a diagnostic and therapeutic challenge for non-specialized physicians, surgeons and other medical doctors. Whereas several specialized centers have gathered data for an improved diagnosis and therapy of neuroendocrine tumor disease, numerous clinical issues have not been resolved on an evidence-based medicine level. Furthermore, the evaluation of new treatment options has been overshadowed by the low incidence of the disease. In this article, a major medical challenge for the diagnosis and therapy of neuroendocrine tumor disease is addressed. As well, new therapeutic treatment options translated from current findings in the fields of molecular and tumor biology are discussed.