The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for alpha 3, alpha 4 and beta 1 integrin chains; negative for alpha 1, alpha 2, alpha 6, beta 3 and beta 4 integrin chains; and heterogeneous for alpha 5, alpha L, alpha M, alpha X, beta 2 and beta 7 integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the alpha L beta 2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (alpha 4 beta 1/VCAM-1 and alpha L beta 2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least alpha L beta 2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.