Late last week fresh rumours on the setting of Assassin's Creed III surfaced over at CVG. According to their source the game will take place during the American Revolution, something that ties into clues in both Assassin's Creed: Brotherhood and Assassin's Creed: Revelations. In a survey Ubisoft issued about where players wanted the third chapter to take place the American Revolution was also an option.
At the very least this change of continents is going to result in a radically different games in terms of environments and architecture, and the gameplay could very well be in for a major change as well.
Furthermore, CVG's source claims that this is going to be the biggest game in the series yet, and that it is going to be announced before March 31.