The relationship between cell surface sialylation and platelet-activating activity was studied in two tumor cell lines of human origin, the SKNMC neuroblastoma line and the U87MG glioblastoma line. Their platelet-activating activity was evaluated in two different experimental systems, one that measures platelet aggregation and the other that quantifies platelet thrombus formation on vascular subendothelium under flow conditions. Our results demonstrate that, for the SKNMC line, the loss of 30% of surface sialic acid induced a significant reduction in its platelet-activating capacity. Upon recultivation desialylated SKNMC cells did not regenerate surface sialic acid and did not restore their initial values of platelet aggregation and platelet thrombus formation. Conversely, removal of 35% sialic acid from the surface of U87MG cells did not affect their pattern of platelet activation in either system tested. These results demonstrate that there is a correlation between cell surface sialylation and the capacity of SKNMC cells to activate platelets. The lack of effect of desialylation on U87MG-induced platelet activation indicates that different surface components may be the modulators of the interactions of these tumor cells with platelets. Our results support the hypothesis that heterologous mechanisms regulate platelet-tumor cell interactions and that tumor cell sialic acid may be only one of the aspects involved in such interactions.