Recently we reported that the N protein of the Old World hantavirus, Hantaan (HTNV), traffics on microtubules to the ER-Golgi intermediate compartment (ERGIC) prior to its movement to the Golgi and requires an intact ERGIC for viral replication. We have extended these studies to the New World hantaviruses, Andes virus (ANDV) and Black Creek Canal virus (BCCV), and an additional Old World hantavirus, Seoul virus (SEOV). These studies support microtubule-dependent trafficking of the N protein to ERGIC within the perinuclear region for the New and Old World hantaviruses. However, we observed that early entry events were distinct for HTNV and ANDV with respect to the pathway for entry and the dependence on an intact actin (ANDV) versus microtubule (HTNV) cytoskeleton for viral replication. These studies show for the first time that while Old and New World hantaviruses share common features in their pathways, they have evolved differences in their interaction with host cell machinery.