With the enhancement of the spatial resolution of satellite imagery (1 m or less), the satellite image analysis has been considered as the indispensable means for remote sensing of nuclear proliferation activities in the restricted access areas such as North Korea. Notably, in the case of an open-pit uranium mine, e.g. the Pyongsan uranium mine, the mining activity can be presumed if detecting the location and extent uranium tailing piles near shafts within temporal images. Several studies have researched on the target detection for minerals of interest such as limestone and coal to evaluate the economic activities by utilizing similarity measures, e.g., a spectral angle mapper and a spectral information divergence (SID). Thus, this paper presented a systematic change detection methodology for monitoring the uranium mining activity in the Pyongsan uranium mine with a similarity measure of SID. The proposed methodology using the target detection results consists of the following five steps. The first step is to acquire stereo images of areas of interest for change detection. The second step is to preprocess the stereo images as following measures: (i) the QUick Atmospheric Correction and the image-to-image registration with ENVI and (ii) the Gram-Schmidt pansharpening. The third step is to extract spectral information for minerals of interest, i.e., uranium tailing piles, by sampling pixels within the reference image. It is based on the satellite analysis report for the Pyongsan uranium mine by CSIS, which specified the location of the uranium tailing piles. As the fourth step, the target detection for uranium tailing piles was performed through the similarity measure of SID between the extracted spectral information and the spectral reflectance of the image. In the fifth step, the change detection was processed using the multivariate alteration detection algorithm, which compares the target detection results by canonical correlation analysis. Furthermore, this paper evaluated the performance of the proposed methodology with the change detection accuracy assessment index, i.e., the area under a receiver operating characteristic curve. In conclusion, this paper suggests the systematic change detection methodology utilizing time series analysis of target detection for uranium tailing piles, which can save time and cost for humans to interpret large amounts of satellite information at the restricted access areas. As future works, the feasibility of the proposed methodology would be investigated by analyzing distribution of minerals of interest regarding nuclear proliferation at Yongbyon, which has the historical events of suspicious nuclear activities.