Abstract: A system and method of producing an image-based registration of an excised tissue specimen for histopathological examination is provided. The method includes: a) producing a three-dimensional image of an excised tissue specimen having a plurality of surfaces at a first location, the excised tissue specimen having an in-vivo orientation prior to being excised; b) producing orientation information relating to the orientation of the plurality of surfaces of the excised tissue specimen relative to the in-vivo orientation of the tissue specimen prior to being excised; c) wherein the excised tissue specimen is transported to a second location and is positioned; and d) using the three-dimensional image and the orientation information to confirm the excised tissue specimen positioned at the second location is in the in-vivo orientation.