Background Endogenous (heterophile, human anti-animal …) antibodies are a known cause of interference in immunoassays. Case report A patient with hypercalcemia and low PTH levels was investigated. The serum 25OH vitamin D (25OHD) concentration was above the analytical range of the automated analyser (> 150 ng/mL) but serum dilutions were not linear. A myeloma-related monoclonal peak of immunoglobulin G (30 g/L) was found. Results Alternative 25OHD assays (RIA, automated analysers, mass spectrometry) all found concentrations < 25 ng/mL. NabTM columns (Thermo Scientific) eliminated the endogenous immunoglobulin from the serum thus allowing the initial analyser to provide correct results. Discussion and conclusion The potentially misleading point was that the apparent very high 25OHD levels were concomitant with hypercalcemia and low PTH levels thus mimicking vitamin D intoxication. Identifying assay interferences requires clinical awareness but, when suspected, one should be aware that technical tools or alternate assays are available to correct some interferences, including monoclonal immunoglobulins.