The processes of isotope fractionation in the hydrological cycle naturally occur during vapor formation, vapor condensation, and moisture transportation. These processes are therefore dependent on local and regional surface and atmospheric physical features such as temperature, pressure, wind speed, and land morphology, and hence on the climate. Because of the strong influence of climate on the isotope fractionation, latitudinal and altitudinal effects on the δ18O and δ2H values of precipitation at a global scale are observed. In this study, we present and compare the processes governing precipitation isotope fractionation from two contrasting climatic regions: Virunga in Central-Eastern Africa and the Central Mediterranean (Stromboli and Sicily, Italy). While Virunga is a forested rainy tropical region located between Central and Eastern Africa, the Mediterranean region is characterized by a rainy mild winter and a dry hot summer. The reported δ18O and δ2H dataset are from precipitation collected on rain gauges sampled either on a monthly or an approximately bimonthly basis and published in previous papers. Both regions show clearly defined temporal and altitudinal variations of δ18O and δ2H, depending on precipitation amounts. The Central Mediterranean shows a clear contribution of local vapor forming at the sea–air interface, and Virunga shows a contribution from both local and regional vapor. The vapor of Virunga is from two competing sources: the first is the continental recycled moisture from soil/plant evaporation that dominates during the rainy season, and the second is from the East African Great Lakes evaporation that dominates during the dry season.