The aim of this paper is to present some research hypotheses and empirical evidence concerning the geographical distribution and spread of leishmaniasis in Greece and particularly in the Greater Athens region, through spatial analysis in a GIS environment. Greece is the WHO Collaborating Center for research and training in Mediterranean zoonoses . Research for leishmaniasis in Greece has indicated that most of the incidents of the disease are concentrated in the Greater Athens region. The results presented in this paper are based on a research project which is currently carried out by the Technological Educational Institution of Athens in collaboration with the University of Crete and the Aristotle University of Thessalonica. The main hypothesis in this paper is that there is a geographical dimension in the diffusion of the disease of leishmaniasis in the Greater Athens region. This dimension includes several environmental factors as indicated in the relevant literature (i.e. elevation, vegetation, meteorological factors, the presence of quarries and dump sites and socioeconomic factors), but also the hypothesis that the incidents of the disease are clustered in the foothills of mountains which surround the Athens Basin, while they tend to follow the urban expansions towards these mountains. Urban expansions in Athens usually include informal settlements. In this paper data concerning urban expansions will be related to the incidents of leishmaniasis for the period 1985-2004. Urban expansions were derived from satellite imagery processing through GIS, while the geographical distribution of the incidents of leishmaniasis is available for the same time period. The results are combined in a geographical database so that the possible interplay among them can be detected employing methods of spatial analysis.