Background:Primary cutaneous follicle center cell lymphomas (PCFCCLs) of the head or trunk have a much better prognosis than morphologically similar large-cell lymphomas on the legs or follicle center cell lymphomas involving the skin secondarily (SCFCCLs). Recent studies suggest a relation between the expression of adhesion molecules and clinical behavior of malignant B-cell lymphomas. Objective: Our purpose was to investigate a potential relation between the expression of adhesion molecules and clinical behavior of these three prognostically different groups of cutaneous B-cell lymphomas. Methods: Immunohistochemical studies with a selected panel of monoclonal antibodies against adhesion molecules were performed on 10 PCFCCLs on the head or trunk, five PCFCCLs of the legs, and seven SCFCCLs. Expression of adhesion molecules was correlated with clinical and follow-up data. Results: PCFCCLs of the head and trunk expressed ICAM-1 (80%) and LFA-1 (50%) much more frequently than PCFCCLs of the legs (40% and 20%, respectively) and SCFCCLs (14% and 14%, respectively). VLA-4 was expressed in 60% of PCFCCLs of the legs, but not by the PCFCCLs of the head or trunk. Absence of both ICAM-1 and LFA-1 on the neoplastic B cells correlated with a poor prognosis (seven of nine patients died of systemic lymphoma). In contrast, none of the patients with expression of LFA-1 or ICAM-1 have died of lymphoma thus far. Conclusion: Our results suggest a relation between the expression of adhesion molecules and the differences in clinical behavior between different groups of primary and secondary cutaneous follicle center cell lymphomas. (J Am Acad Dermatol 1997;37:34-40.)