Recently, there have been substantial advances in techniques to detect, measure and characterize monoclonal gammopathies. For example, capillary zone electrophoresis can crisply separate serum components, detecting subtle monoclonal proteins. In addition, immunosubtraction (immunotyping) can aid in measuring M-proteins that co-migrate with other serum proteins. However, there interferences can result from a variety of substances including antibiotics and radiocontrast dyes. By use of real time audience response systems a variety of challenging and instructive cases will demonstrate the problems of false positive and false negative tests. The information will be synthesized into a practical approach to effective and efficient detection of M-proteins.