Tumor cell migration requires a coordinated formation and release of focal adhesion contacts to the extracellular matrix mediated by integrin receptor molecules. As shown by in vitro studies and cell adhesion assays, binding of integrin dimers to the extracellular matrix is affected by divalent cations. Mn²⁺ and Mg²⁺ have a stabilizing effect on the integrin/matrix bond which is counteracted by Ca²⁺ and Zn²⁺. The present study focuses on the effect of Mn²⁺ on migration and morphology of human melanoma cells (MV3) measured at different extracellular pH values (pH_e 6.8 and 7.2). Cells were faster at pH_e 7.2 regardless of the presence of Mn²⁺. Mn²⁺ treated cells migrated more slowly than the controls. At pH_e 7.2 cells showed a rather spherical, at pH_e 6.8 a rather dendritic morphology. Addition of Mn²⁺ led to a more spherical cell shape accompanied by a decrease of the lamellipodia length. Mn²⁺ had no effects on cell adhesion implying that adhesion of MV3 cells is mediated by molecules other than integrin dimers. Although there were no detectable effects on adhesion, Mn²⁺ causes a decrease in migratory speed. These findings suggest that the Mn²⁺ dependent stabilization of the matrix/collagen bond, for example the a2b1 integrin/collagen bond, inhibits the growth of lamellipodia and therefore cell migration.