The development of cancer proceeds through a number of stages in which the transformed cells increase their potential for autonomous growth and invasiveness. Our knowledge of the early stages of this tumor progression process have been greatly enhanced by the analysis of oncogenes, particularly the components and processes involved in producing the transformed state (Hunter, 1991). Much less is understood about the latter stages of tumor progression toward invasiveness and metastasis (Liotta et al., 1991), even though these processes are clearly the critical elements in cancer. Many of the steps involved in progression result in changes at the tumor cell surface, including decreased adhesiveness, increased degradative capabilities, altered motility and altered antigenicity. This plethora of cell surface effects is very complex and varies with different tumors. However, one of the common characteristics of tumors and tumor progression is the altered expression of cell surface complex carbohydrates. These changes include the increased size of N-linked oligosaccharides that occurs with transformation (Warren et al., 1978), the expression of blood group-related oligosaccharides on both glycoproteins and glycolipids (Singhal and Hakomori, 1990), and the expression of incomplete or truncated mucin-type oligosaccharides (Springer, 1984). In this article we will discuss one class of complex carbohydrate which has been implicated in tumor progression, the tumor cell sialomucin. Recent studies have begun to define the complexities of both the structures and functions of these molecules. Sialomucins are large, heavily O-glycosylated molecules (Carraway and Hull, 1991). In tumor cells two types of sialomucins have been observed. One class is released from the tumor cells; the second is on the cell surface as a heterodimeric complex composed of a transmembrane subunit and a mucin-like subunit (Fig. 1)(Codington and Frim, 1983; Carraway and Spielman, 1986; Carraway and Hull, 1991). The mucin subunit of the complex extends in a rod-like structure from the cell surface, providing a protective barrier to the cell membrane. Part of the mucin-like subunit of these complexes may also be released from the cell. Our thesis is that the over-expression of these cell surface glycoprotein complexes can provide to tumor cells several attributes which are important to tumor progression. Included among these attributes are the ability of sialomucins to act as an anti-recognition factors and, in some cases, of the transmembrane component to serve as a growth factor which can provide a mechanism for autonomous tumor cell proliferation. Thus, mucin overexpression, when it occurs, can serve as one of several factors promoting tumor progression. The potential importance of tumor cell surface sialomucins was first recognized in the mouse TA3 mammary adenocarcinoma (Codington et al., 1972). Allotransplantable ascites sublines of this tumor were found to have abundant amounts of a cell surface sialomucin, named epiglycanin, which was absent from non-allotransplantable sublines (Codington and Frim, 1983). Subsequent studies on ascites 13762 rat mammary adenocarcinoma cells identified and characterized a similar sialomucin (Carraway et al., 1978), ascites sialoglycoprotein-1 (ASGP-1)(Sherblom et al., 1980). These sialomucins are proposed to protect the tumor cells from the immune system of their host, epiglycanin by blocking recognition of the histocompatibility complex (Codington and Frim, 1983) and ASGP-1 by providing resistance to destruction by natural killer cells (Moriarty et al., 1990). In 13762NF cultured cells selected for metastatic capacity …