Remodeling of actin and microtubule cytoskeletons is thought to be coupled; however, the interplay between these two systems is not fully understood. We show a microtubule end-binding protein, EB1, is required for formation of polarize morphology and motility of melanoma cells. EB1 depletion decreased lamellipodia protrusion, and resulted in loss of opposed protruding and retracting cell edges. Lamellipodia attenuation correlated with mis-localization of filopodia throughout the cell and decreased Arp3 localization. EB1-depleted cells displayed less persistent migration and reduced velocity in single-cell motility experiments. We propose EB1 coordinates melanoma cell migration through regulating the balance between lamellipodial and filopodial protrusion.