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A methodology of investigation and diagnosis on the built patrimony of historic centres in seismic areas is presented with the aim of collecting an extensive knowledge on the structural typologies and behaviour of historic masonry buildings. This investigation is also the base for the prevention and/or repair of damages caused by earthquakes. Small historic centres or residential buildings in larger centres have been considered for long time as “minor architecture”, but they are meaningful testimonies of the local cultural heritage and express the evolution of a society and of its cultural identity. The results of the investigation carried out on different Italian historic centers, allowed also a critical review of the reliability of the analytical models and of the effectiveness of the repair techniques applied in the past decades. The guidelines emerging from the research results are here presented. A “minimal” diagnostic investigation program is also suggested, in order to support the designers in their projects and to set up appropriate mathematical models to study the vulnerability of the structures.