Systems and methods for managing positioning assistance data for large regions are described herein. An example of a method for retrieving positioning assistance data at a mobile device as described herein includes identifying a master region in which the mobile device is located and sub-region definitions associated with the master region, where the sub-region definitions are indicative of area occupied by the sub-regions within the master region; obtaining a first estimated position of the mobile device within the master region; defining a projected area centered at the first estimated position; and obtaining first assistance data corresponding to at least one sub-region that overlaps the projected area.