Observed climate change has already led to awide range of impacts on environmental systems and society. In this context, many mountain regions seem to be particularly sensitive to a changing climate, through increases in temperature coupled with changes in precipitation regimes that are often larger than the global average (EEA, 2012). In mid-latitude mountains, these driving factors strongly influence the variability of the mountain snow-pack, through a decrease in seasonal reserves and earlier melting of the snow pack. These in turn impact on hydrological systems in different watersheds and, ultimately, have consequences for water management. Snow monitoring from remote sensing provides a unique opportunity to address the question of snow cover regime changes at the regional scale. This study outlines the results retrieved from the MODIS satellite images over a time period of 10 hydrological years (2000–2010) and applied to two case studies of the EU FP7 ACQWA project, namely the upper Rhone and Po in Europe and the headwaters of the Syr Darya in Kyrgyzstan (Central Asia). The satellite data were provided by the MODIS Terra MOD-09 reflectance images (NASA) and MOD-10 snow products (NSIDC). Daily snow maps were retrieved over that decade and the results presented here focus on the temporal and spatial changes in snow cover. This paper highlights the statistical bias observed in some specific regions, expressed by the standard deviation values (STD) of annual snow duration. This bias is linked to the response of snow cover to changes in elevation and can be used as a signal of strong instability in regions sensitive to climate change: with alternations of heavy snowfalls and rapid snow melting processes. The interest of the study is to compare the methodology between the medium scales (Europe) and the large scales (Central Asia) in order to overcome the limits of the applied methodologies and to improve their performances. Results show that the yearly snow cover duration increases by 4–5 days per 100 m elevation during the accumulation period, depending of the watershed, while during the melting season the snow depletion rate is 0.3% per day of surface loss for the upper Rhone catchment, 0.4%/day for the Syr Darya headwater basins, and 0.6%/day for the upper Po, respectively. Then, the annual STD maps of snow cover indicate higher values (more than 45 days difference compared to the mean values) for (i) the Po foothill region at medium elevation (SE orientation) and (ii) the Kyrgyzstan high plateaux (permafrost areas). These observations cover only a timeperiod of 10 years, but exhibit a signal under current climate that is already consistentwith the expected decline in snow in these regions in the course of the 21st century.