Objective: Unusual clinical course Background: Hepatitis C Virus (HCV)-related chronic hepatitis can be associated with mixed cryoglobulinemia (MC). Although several MC cases have been described, the wide variety of symptoms often makes diagnosis challenging. Case Report: We describe a sudden onset of coma in a 70-year-old woman with an undiagnosed chronic hepatitis C infection related to MC. Head CT did not show any important pathology. Laboratory tests showed leucocytosis, but it was not possible to identify any pathogenic microorganism. Examination of cerebrospinal fluid did not show any pathology. There was a strongly positive test result for rheumatoid factor (409 U/l) and hypocomplementemia (C4 0.04 g/l). Laboratory assay was positive for antibodies against HCV and HCV RNA. The cryoglobulins were positive and after treatment with plasmapheresis her conditions improved. Conclusions: In this case, the cryoglobulins laboratory exam was very helpful for the diagnosis. This test could be considered in the early management of elderly patients with sudden onset of coma. © Am J Case Rep, 2014.