Factor XIII (plasma transglutaminase, fibrin stabilizing factor) is a glycoprotein that circulates in blood as a tetramer, consisting of two A and two B subunits. Subunit A of factor XIII is an un-glycosylated 730-residue peptide with a molecular mass of 83 kD. It is the last enzyme generated in the blood coagulation cascade and is the zymogen for fibrinoligase, a transglutaminase that forms intramolecular gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules and thus stabilizes blood clots. Factor XIII A is present in plasma, platelets, and monocytes, as well as macrophages and bone marrow precursors of these cell types and selective expression in subsets of stromal inflammatory cells. Factor XIII A is a marker for alternatively activated macrophages, while absence of Factor XIII A in monocyte-derived macrophages is an indicator of their activated state. In addition, Factor XIII A is useful in distinguishing malignant fibrous histiocytoma (positive) from soft tissue tumor (negative).