Human IgG4 accounts for less than 6% of the total IgG serum level. Recent studies show that serum levels and immunohistochemistry staining with IgG4 antibody is a useful diagnosis marker for IgG4-related sclerosing diseases. A new concept of IgG4-related systemic disease (ISD) has been established recently. The ISD is characterized by elevated serum IgG4 levels and extensive IgG4+ plasma cell infiltrate in pancreas and/or in other organs, including peripancreatic tissue, bile duct, gallbladder, portal area of the liver, gastric mucosa, colonic mucosa, salivary glands, lymph nodes, and bone marrow. Immunohistochemistry analysis of IgG4 is useful for identifying ISD.