A method and apparatus for locating an internal target region during treatment without implanted fiducials is presented. The method comprises producing a plurality of first images that show an internal volume including the internal target region, then producing a live image of the internal volume during treatment and matching this live image to one of the plurality of first images. Since the first images show the internal target region, matching the live image to one of the first images identifies the position of the target region regardless of whether the second image itself shows the position of the target region. The first images may be any three-dimensional images such as CT scans, magnetic resonance imaging, and ultrasound. The live image may be, for example, an x-ray image. The invention may be used in conjunction with a real-time sensor to track the position of the target region on a real-time basis.