It has been appreciated for quite some time that a "round cell" inflammatory infiltrate is present in the dermis during the early stages of scleroderma. Considerable research has emanated from this basic observation, with the assumption that interactions between immune cells and fibroblasts are paramount in the genesis of fibrosis. The large number of mast cells that accumulate early in involved tissues has been less appreciated in recent studies. The purpose of this update is to demonstrate how mast cells interact with fibroblasts in a manner that leads to fibroblast activation and subsequent extracellular fibrosis. Furthermore, the notion that myofibroblasts represent a critical fibroblast phenotype in sclerosing disorders, such as scleroderma, has also gained considerable support. The relationship of tissue mast cells to the generation of a myofibroblast phenotype has been the focus of several recent reports and will also be discussed.