The hyperviscosity syndrome has been described clinically as the triad of bleeding, visual signs and neurological manifestations associated with elevated serum viscosity. Several reports have recognised an association between hyperviscosity and altered mental status. Since to our knowledge only a case of hyperviscosity-induced delirium has been described (1), we raise the possibility of this diagnosis in the most of this reported cases, based on the nature of the symptoms, sudden onset and fluctuating course, and its resolution with plasmapheresis. In this paper we review the literature about hyperviscosity syndrome and altered mental status. In conclusion, serum hyperviscosity should be added to the large list of causes altered mental status, especially of delirium. Since plasmapheresis can reverse clinical symptoms, it early recognition and the measurement of serum viscosity is essential in patients suffering from diseases that may lead to this syndrome, and who develop psychiatric symptoms.