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Objectives Cryoglobulins (CGs) are serum proteins that undergo a reverse cold-induced precipitation  in vitro . The CGs are a well-known cause of analytical interferences in several laboratory tests, leading to spurious results. With this in view, we present a case of a patient initially misdiagnosed due to CGs interference in Hepatitis C Virus (HCV) serology. Case presentation We report a case of a woman of advanced age affected by acute renal failure that required urgent haemodialysis. In the absence of infections and other causes of CGs production, a diagnosis of acute renal failure secondary to essential cryoglobulinemia was established. However, an unexpected positive HCV viral load was encountered. At this point, a false-seronegative HCV infection conditioned to CGs interference  in vitro  was suspected, confirmed by repeating serology in pre-warmed serum. Finally, the patient was correctly diagnosed with HCV-secondary cryoglobulinemia. Conclusions As shown in the case, the presence of CGs in blood may represent a challenge for the correct interpretation of several laboratory tests. The identification of CGs and the pre-treatment of serum are decisive to avoid spurious results and reach a genuine diagnosis.

False-seronegative HCV infection motivated by interference with cryoglobulins