Well-defined locations of pemphigus cases support the hypothesis of environmental factors' involvement in its etiopathogenesis; however, these foci have never been described using specialized geographical tools. This is the first report to geo-reference pemphigus cases in a high-prevalence Brazilian region using geographic information systems. We aimed to report the spatio-temporal behavior of pemphigus foliaceus (PF) and vulgaris (PV) in southeastern Brazil, over the last five decades to describe geographical clusters, as well as to characterize the land use in the city with the highest number of cases. Patients were identified from 1965 to 2014. Maps were developed using ArcGIS software and organized into decades from 1965 to 2014. Ribeirão Preto was identified as the city with the greatest number of cases. Land use was analyzed within a 2 km-buffer surrounding the residence of each patient. A total of 426 cases of pemphigus were identified. PF was the predominant form (285 cases); notwithstanding, the number of new cases of PV rose, overtaking the number of new cases of PF in the last decade studied. Agricultural area (42%) and exposed soil (33.2%) are the most predominant land uses in Ribeirão Preto surrounding patients' residences. This study shows high-confidence geographical foci of PF and PV, as well as provides evidence of an increase of both clinical forms over the last five decades. All cases of PV and PF are in proximity to rivers and agricultural areas which reinforce the hypothesis that environmental factors play a role in pemphigus etiopathogenesis.