The extracellular matrix protein, laminin, supports platelet adhesion through binding to integrin α₆β₁ In the present study, we demonstrate that human laminin, purified from placenta, also stimulates formation of filopodia and lamellipodia in human and mouse platelets through a pathway that is dependent on α₆β₁ and the collagen receptor GPVI. The integrin α₆β₁ is essential for adhesion to laminin, as demonstrated using an α₆-blocking antibody, whereas GPVI is dispensable for this response, as shown using “knockout” mouse platelets. On the other hand, lamellipodia formation on laminin is completely inhibited in the absence of GPVI, although filopodia formation remains and is presumably mediated via α₆β₁ Lamellipodia and filopodia formation are inhibited in Syk-deficient platelets, demonstrating a key role for the kinase in signaling downstream of GPVI and integrin α₆β₁ GPVI was confirmed as a receptor for laminin using surface plasmon resonance spectroscopy and by demonstration of lamellipodia formation on laminin in the presence of collagenase. These results identify GPVI as a novel receptor for laminin and support a model in which integrin α₆β₁ brings laminin to GPVI, which in turn mediates lamellipodia formation. We speculate that laminin contributes to platelet spreading in vivo through a direct interaction with GPVI.