Abstract: Implementations described herein relate to an anatomical referencing system and associated methods for surgical navigation that include referencing shapes and features on excised target tissue back to the wound or cavity in the body from which it was removed. Such an anatomical referencing system can comprise an expandable structure operably coupled to a controller assembly. The expandable structure can have a port in communication with an interior cavity and a surface adapted for measuring having a plurality of navigation markers. The controller assembly can operate to communicate with the expandable structure through the port and can have a means for expanding the expandable structure to a selected pressure against the cavity. The expandable structure can be adapted to conform to the geometry of the cavity in which it is placed upon expansion by the controller assembly. The controller assembly can include a means for recording the dimensions of the interior cavity of the expanded structure.