The ultrastructural localization of an amorphous matrix to the interface between microvessel endothelium and tumor cells has been recently reported in a series of melanomas. Laminin expression as documented by immunohistochemistry was localized to microvessels in melanomas showing the amorphous matrix. In order to identify more precisely the type of laminin present in this amorphous material, immunostaining was carried out on cryostat sections from 16 human melanoma specimens. Four murine monoclonal antibodies directed against the alpha-3, beta-2, beta-3 and gamma-2 laminin chains were employed. In the melanomas studied, alpha3, beta3 and gamma2 laminin chains showed only minimal focal vascular positivity. In contrast, the beta2 (16/16 cases) laminin chain exhibited a consistent positivity in an angiocentric pattern about tumor microvessels. In all melanomas, some tumor cells seemed to spread along the abluminal surface of the small vessels, exhibiting a pericytic location, particularly along the intratumoral projections formed by the beta2 laminin chain. Given the role of laminin in migration and tumor progression, the results suggest a role of the beta2 laminin chain in melanoma spread, promoting tumor migration along the abluminal surface of vessel, a phenomenon which has been termed extra-vascular migratory metastasis.