Syndrome of inappropriate antidiuresis (SIAD) is a common paraneoplastic syndrome commonly associated with thoracic malignancies, gastrointestinal cancers and kidney tumors. It is defined as hyponatremia in euvolemic patients, often due to abnormal secretion of antidiuretic hormone by tumor cells. Tolvaptan, a vasopressin-2-receptor antagonist, is currently recommended for patients affected by SIAD with mild or moderate symptoms. Among patients with prostatic cancer, SIAD represents a rare condition but it is frequently associated with poorly differentiated adenocarcinoma or pure small-cell carcinoma histotype. We report a case of SIAD appeared at disease progression in a 60-year-old male patient with acinar adenocarcinoma with neuroendocrine differentiation together with a literature review.