Waldenstrom's macroglobulinemia (WM) is an indolent B-cell lymphoma of the lymphoplasmacytic type accompanied by a serum IgM component. However, conventional IgM quantification lacks sensitivity, does not precisely reflect tumor burden of WM, and, although being the main marker for monitoring response to treatment, may not be accurate. New serum M-component based biomarkers were developed for routine practice in recent years, such as the Freelite® test and more recently the Hevylite test®. Studies have shown that Freelite was a prognostic marker for time to treatment in WM that helps monitoring disease response or progression. Hevylite measures IgMkappa and IgMlambda, separately, and might provide true quantitative measurement of the IgM M-spike. Although current data are preliminary, Hevylite® might replace the current technique to measure IgM M-spike in the years to come. We summarize herein studies conducted to delineate the role of these tests in WM.