β2-microglobulin (B2M) plays a vital role in cell survival, proliferation and metastasis in various types of cancer. Elevated concentration of β-2-microglobulin (B2M) can be considered as a prognostic marker for hemophagocytic lymphohistiocytosis (HLH). Elevated concentration of circulating B2M, due to renal dysfunction and long term hemodialysis, leads to dialysis-related amyloidosis. Overexpression of serum B2M is observed in hepatitis C virus (HCV) related chronic liver diseases, therefore it might act as a potential marker for the HCV disease progression towards cirrhosis and carcinoma. Missense mutation in the B2M gene results in familial hypercatabolic hypoproteinemia (FHH).