A method and system for navigation of a medical instrument, including: introducing at least three reference device(s) disposed to at least three reference locations; employing an imaging and guidance system to acquire a plurality of image projections corresponding to a desired anatomy including the reference devices, the plurality of image projections being sufficient to permit generating a three-dimensional modeling or reconstruction images corresponding to the reference devices. The method also includes measuring a position of the reference devices; formulating a transformation matrix based on comparing positions of the reference devices computed from the modeling or reconstruction images with the measured positions of the reference devices; and superimposing an image of a medical instrument in at least one of the plurality of image projections based on the transformation matrix and a position of the medical instrument.