Fibronectin plays a major role in the adhesion of many cell types. The extent of cell adhesion in vitro is related not only to the ability of the cells to interact with matrix-bound fibronectin, when it is present, but also to the synthesis or lack of synthesis of fibronectin by the cells, and to the lack of deposition of synthesized fibronectin into an insoluble matrix surrounding the cells. Many malignant cells, regardless of whether they synthesize subnormal or normal amounts of fibronectin, fail to deposit that fibronectin into a surrounding insoluble matrix. The lack of fibronectin around such cells appears to reflect a general absence of extracellular matrix since other matrix components, such as collagen, laminin, and heparan sulfate proteoglycan, are concomitantly missing. Cells that lack their own cell surface fibronectin due either to lack of deposition or to lack of synthesis can nevertheless adhere to insoluble fibronectin matrices elaborated by other cells. These cellular characteristics appear to be associated with cell migration in vivo during embryogenesis, and the same characteristics may enhance the invasive potential of malignant cells. The remarkable effects that fibronectin has on cellular adhesion and the association of lack of extracellular matrix components with poorly differentiated and highly metastatic tumors in vivo mandates that more be learned about the molecular and cellular details of the interactions of cells with their surrounding matrix. Important information concerning tumor invasion will parallel such an understanding and may eventually become the basis for therapeutic approaches.