We present an application of digital image processing techniques in medieval mosaic conservation. The reconstructed art piece was The Last Judgment mosaic, situated on the wall of the St. Vitus cathedral in Prague, in the Czech Republic. The historical photograph of the mosaic from the 19th century was compared with the photograph of the current state in order to detect mutual differences. The images were firstly pre-processed to increase their quality (noise reduction, deblurring). In the second stage, geometrical differences between images were removed by means of image registration techniques—mutual information and feature point correspondence. Finally, differences of the current and historical photographs were identified.