<p>Neuroendocrine neoplasms (NENs) are a particular diagnostic and therapeutic challenge due to their marked heterogeneity. In addition to their highly variable tumor biology—ranging from indolent, low-proliferative neuroendocrine tumors to highly aggressive neuroendocrine carcinomas—the clinical presentation also varies widely. They are often nonspecific and clinically difficult to classify, but in some cases may also present with a characteristic, hormone-associated tumor syndrome. In light of this, tumor markers play a central role, both in establishing a diagnosis and in assessing prognosis and response to therapy. At the same time, their use is fraught with significant limitations that can lead to misinterpretations, misguide therapeutic decisions, and contribute to patient uncertainty. This article demonstrates how tumor markers can be used in a meaningful way for NENs and highlights the typical sources of errors to be aware of.</p>