Calcium pyrophosphate dihydrate (CPPD) deposition disease is a relatively common condition primarily affecting the elderly. Various clinical presentations ranging from an acute arthritis resembling gout (pseudogout) to fever of unknown origin have been reported.We describe four elderly patients with fever and altered mental status. Each patient underwent an extensive unrevealing work-up. An acute arthritis missed by the health-care team in their initial evaluation was later identified, leading to rheumatologic consultation and subsequent diagnosis of CPPD disease after joint aspiration and synovial fluid analysis. Defervescence and resolution of mental status changes occurred after improvement of the arthritis.Awareness that CPPD disease may present with systemic symptoms, including fever and altered mental status, may assure careful examination of joints and can prevent unnecessary testing and diagnostic delay.