Human immunodeficiency virus (HIV) is a major global health problem. Infection with this virus leads to humoral immune dysregulation that can span the gamut from benign polyclonal hypergammaglobulinemia to multiple myeloma. Epidemiologic studies have demonstrated that patients with HIV are at increased risk for the development of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma, which occur at younger ages compared to the rest of the population. Interpretation of serum protein electrophoresis (SPEP) and immunoelectrophoresis (IEP) results in patients with HIV can be challenging. We present a case of a 66-year-old HIV-positive male with intermittent prior highly active retroviral treatment (HAART) therapy who was found to have an IgG lambda monoclonal band on SPEP and IEP in the background of polyclonal hypergammaglobulinemia. A follow-up bone marrow biopsy demonstrated marked plasmacytosis without evidence of a plasma cell neoplasm. This case highlights the challenges of interpretation of SPEP and IEP results in this setting and highlights the importance of awareness of these potential pitfalls to avoid overdiagnosis and subsequent overtreatment.