Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as ‘invasive growth’, which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA‐MB‐231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3‐K‐dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function‐blocking antibodies show that this phenomenon is mediated by multiple integrins including βl, β3, β4, and β5. HGF/SF triggers clustering of all these integrins at actin‐rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.–Trusolino, L., Cavassa, S., Angelini, P., Andò, M., Bertotti, A., Comoglio, P. M., Boccaccio, C. HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity. FASEB J. 14, 1629–1640 (2000)