This presentation focuses on contemporary methods for detection of monoclonal proteins (M-protiens) that are associated with multiple myeloma and other plasma cell dyscrasias. The basic principles of the techniques currently used will be presented along with a triage that can be used for their implementation. None of the techniques is without the hazards of false positive and false negative results. When using serum protein electrophoresis as the screen, the main causes for false positives include the presence of fibrinogen and genetic variants of normal serum proteins. When capillary electrophoresis is used to screen serum, radiocontrast dyes and some antibiotics can mimic M-proteins. False negatives occur because will be demonstrated along with tactics to prevent them. Serum free light chain testing is a boon to detecting multiple myeloma without requiring a 24 hour urine sample, however the user needs to be aware of the high-dose hook effect which can produce falsely low results. The newest serologic test is able to measure heavy and light chain specific pairs, i.e. distinguishing between populations of IgG kappa and IgG lambda. These reagents may aid in classification and risk stratification, but more independent research will be needed to determine their utility.