Neoplastic fever, a paraneoplastic syndrome caused by cancer itself, represents a diagnostic challenge for the clinician and is an important issue in supportive oncology. Timely recognition of this febrile condition by differentiating it from other cancer-associated fevers, such as infection and drug reaction, is essential for effective patient management. Although the pathophysiology of neoplastic fever is not well understood, it is suspected to be cytokine mediated. In clinical practice, when a patient with cancer presents with unexplained fever, extensive diagnostic studies are needed to differentiate neoplastic fever from nonneoplastic fever. Only after excluding identifiable etiologies of fever can the diagnosis of neoplastic fever be suspected. According to our experience, the naproxen test is a safe and useful test in differentiating neoplastic fever from infectious fever in patients with cancer. In addition, naproxen and other nonsteroidal anti-inflammatory drugs have been effective in the management of neoplastic fever and offer a significant palliative benefit for the patient.