Preanalytical irregularities in serum separator tubes are frequently regarded as technical artifacts. In this case, repeated failure of serum separation led to the diagnosis of multiple myeloma. A 77-year-old woman presented with chest pain and fatigue, and successive serum samples failed to form an adequate gel barrier, yielding only minimal serum despite prolonged centrifugation. Biochemical analyses revealed hypoalbuminemia, elevated total protein, increased IgA with suppressed IgM and IgG levels, and a markedly decreased kappa/lambda ratio. Serum and urine immunofixation identified an IgA–lambda monoclonal band. PET-CT demonstrated multiple lytic bone lesions. Bone marrow biopsy revealed a hypercellular marrow with 80% plasma cell infiltration, confirming the diagnosis of multiple myeloma. These findings underscore that abnormal serum separation, often dismissed as a technical issue, may serve as an early indicator of underlying hematologic malignancy.