This brief review details the structure, nature, and distribution of the fibronexus, and discusses its significance for myofibroblastic differentiation and tumor diagnosis. The fibronexus is a cell surface specialization consisting of intracellular actin filaments and extracellular fibronectin filaments associated with subplasmalemmal plaque material. The fibronexus represents an intercellular junction between myofibroblasts, but in particular is a device for providing contact between myofibroblasts and matrix that mediates continuity between intracellular contractile filaments and extracellular matrix proteins. Immunoelectron microscopy in particular has shown that the intracellular filaments contain actin. The extracellular filaments contain fibronectin and collectively form the fibronectin fibril. The plaque probably contains such proteins as vinculin, talin, alpha-actinin, and integrin. Under appropriate biologic development and fixation conditions, the fibronectin fibril of the fibronexus is characterized by and distinguished from lamina by enhanced density, a rigid appearance, failure to adhere closely to the contours of the cell surface (except focally near the plaque material), and a longitudinally filamentous substructure. Confirmation of the presence of a fibronectin fibril may be obtained by the finding of intense cell surface staining with an antifibronectin antibody. Problems in identifying the fibronexus may be encountered, however, due to poor development and fixation, in which case the filamentous substructure may be inapparent. The fibronexus is such a typical feature of and is often so conspicuous in myofibroblasts that it can be regarded as perhaps essential for the interpretation of myofibroblastic differentiation. Structures with a similar appearance have been documented in fundamentally nonmyofibroblastic cells; these include aortic and scleral spur smooth muscle cells and endothelium. Uncertainties remain in the protein composition of the fibronexus, the nature of its contact with the matrix, and its relationship to similar structures seen in nonmyofibroblastic cells. Immunoelectron microscopy provides a potential means of clarifying some of these questions.