Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein in the immunoglobulin superfamily, which plays an important role in cell adhesion and signal transduction. Although ICAM-1 is believed to play a role in several malignancies, it is still uncertain whether or not ICAM-1 expression contributes to cancer progression. In this study, we performed clinicopathological and cell biological analyses of ICAM-1 expression in oral squamous cell carcinoma (SCC). First, we examined the ICAM-1 expression in tongue SCC immunohistochemically, and revealed that ICAM-1 was expressed predominantly at the invasive front area of tongue SCC. ICAM-1 expression at the invasive front area was correlated with invasion, lymph node metastasis, and increased blood and lymphatic vessel density of the tongue SCC. The relationship between ICAM-1 expression and clinicopathological factors were consistent with the increased proliferation, invasion, and cytokine-production activities of ICAM-1-transfected SCC cells. Second, we analyzed the relationship between macrophages and ICAM-1-expressing tongue SCC cells because ICAM-1 is known to act as a ligand for adhesion of immune cells. Increased ICAM-1 expression in tongue SCC was correlated with increased macrophage infiltration within SCC nests. Moreover, macrophage/SCC-cell adhesion through ICAM-1 molecule was revealed using an in vitro cell adhesion and blockade assay. These findings indicate that ICAM-1 plays an important role in tongue SCC progression, which may result from the SCC-cell activity, angiogenic activity, lymphangiogenic activity, and macrophage/SCC-cell adhesion.