Methods and systems for image alignment are provided. One method includes selecting three or more salient feature points for use in test image to reference image alignment by applying a selected salient feature point detection method to at least a reference image generated for the specimen. The method also includes detecting the three or more salient feature points in the test image and the reference image and aligning the detected three or more salient feature points in the test image to the detected three or more salient feature points in the reference image. The method further includes aligning remaining portions of the test image to remaining portions of the reference image based on results of the previous aligning step.