In approximately 13% of patients who are diagnosed as having neuroendocrine tumors (NETs), the primary site is not known.1 Commonly, biopsy of a liver mass reveals an NET metastasis; in other instances, a lymph node metastasis is found on biopsy of a mesenteric, retroperitoneal, or peripancreatic mass. However, a primary tumor remains elusive. The topic of NETs of unknown primary site perplexes even those experienced in NETs because it raises 5 key questions, each of which we attempt to answer here.