A Regional Climate Change Index (RCCI), is developed based on regional mean precipitation change, mean surface air temperature change, and change in precipitation and temperature interannual variability. The RCCI is a comparative index designed to identify the most responsive regions to climate change, or Hot-Spots. The RCCI is calculated for 26 land regions from the latest set of climate change projections by 20 global climate models for the A1B, A2 and B1 IPCC emission scenarios. The Mediterranean and North Eastern European regions emerge as the primary Hot-Spots, followed by high latitude northern hemisphere regions and by Central America, the most prominent tropical Hot-Spot. The main African Hot-Spots are Southern Equatorial Africa and the Sahara. Eastern North America is the prominent Hot-Spot over the continental U.S. Different factors over different regions contribute to the magnitude of the RCCI, which is in fact greater than 0 for all regions.