A method for positioning a tip of an atomic force microscope relative to a intracellular target site in a cell is provided. In general terms, the method comprises: a) positioning a fluorescent tip of an atomic force microscope over a cell comprising a fluorescent intracellular target site so that said tip is above target site; b) moving the tip toward said target site while obtaining images of the distal end of said tip and/or the target site using a fluorescence microscope; and c) arresting the movement of the tip when the target site and the distal end of the tip are both in focus in the fluorescence microscope. A microscope system for performing the method is also provided.