Neuroendocrine neoplasms (NENs) are rare malignancies that arise from neuroendocrine cells present in various organs, most commonly of the digestive tract. They often present with metastatic disease, particularly in the liver, and in approximately 10–14% of cases, no primary tumor can be identified thought conventional diagnostic imaging techniques. This condition, known as NEN of unknown primary (NEN-UP), requires a dedicated multidisciplinary team management. Determining the primary tumor site involves multiple steps including to assess the clinical presentation, especially the cases with hormonal functional syndrome, along with immunohistochemical (IHC) staining and a comprehensive morphological and functional imaging work-up. The prognosis for metastatic NEN-UP is generally poorer than for metastatic NENs with a known primary site. However, radical surgery may offer a favorable therapeutic approach even in NEN-UP cases.