Factor XIII, a transglutaminase whose best-known function is in the coagulation cascade, is widely distributed in tissues. Three patterns of expression are found in the skin: (1) in cells in an angiocentric pattern around superficial vessels, (2) in early reparative lesions that result in fibroplasia, and (3) in certain sessile neoplasms. Around superficial vessels factor XIII probably stabilizes fibrin clots and helps to seal superficial wounds. On the basis of patterns of expression in evolving reparative lesions, factor XIII likely has an important but still undefined function in the development of fibroplasia. Factor XIII's proposed role in the promulgation of fibroplasia would be integral to the production of the stromal component of small neoplasms that is known to be associated with factor XIII expression.