Paraproteins have been reported to cause interference in a sort of chemistry assays conducted by current automated chemistry analyzers. However, the nature of interference differs across different methodologies and reactions. Total bilirubin and direct bilirubin assays might yield spurious result when the sample contains excess amounts of paraproteins, which are neither reliable nor reproducible when repeated tests are applied once the interference occurs. Herein, we present the case of a 78‑year‑old female diagnosed with kappa light chain multiple myeloma with disease progression. On admission, she had acute hepatitis and a bizarre result with direct bilirubin level higher than total bilirubin level was noted. After further investigation, excess amounts of immunoglobulin G (IgG) were the most likely cause which led to the interference of direct bilirubin assay and caused unreliable results. This case highlights the significance of the fact that patients with excess IgG might have unreliable results of direct bilirubin assay which could mislead clinical judgment. Moreover, clinicians should be more careful and should base therapeutic decisions on the patient’s clinical condition when faced with patients in a similar condition.