A panel of monoclonal and polyclonal antibodies raised against human platelet GpIb or the GpIIb/IIIa complex were used to detect immunologically related molecules on two cell lines derived from human solid tumors. Human cervical carcinoma (MS751) and human colon carcinoma (clone A) expressed molecules immunologically related to platelet GpIb and GpIIb/IIIa complex. These molecules were localized to their plasma membranes by immunofluorescence and immunocytochemistry. The immunologically related GpIb was evenly distributed on the tumor cell membrane with occasional areas of aggregates, whereas the immunologically related GpIIb/IIIa had a pronounced punctate distribution of aggregates in prefixed cells. When MS751 or clone A cells were pretreated with antibodies against platelet GpIb and/or the GpIIb/IIIa complex, their ability to induce platelet aggregation was significantly inhibited. In addition, when tumor cells were pretreated with antibodies against the platelet IIb/IIIa complex, adherence to fibronectin‐coated plates was also significantly inhibited. These results suggest a role for these immunologically related tumor cell glycoproteins in tumor cell‐host cell (i.e., platelet, endothelial cells) interactions, tumor cell interactions with components of the subendothelial matrix, and subsequent tumor metastasis.—Grossi, I. M.; Hatfield, J. S.; Fitzgerald, L. A.; Newcombe, M.; Taylor, J. D.; Honn, K. V. Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and Ilb/IIIa in tumor cell‐platelet and tumor cell‐matrix interactions.FASEB J.2: 2385‐2395; 1988.