The present paper deals with the elaboration of a methodology to assess the macro-seismic risk of monumental historical buildings, representing a fundamental part of the European cultural assets. Monumental buildings typically arise from a very complex constructive and morphological evolution process characterised by modifications occurred over the centuries. Therefore, they are usually heterogeneous buildings similar to 'structural aggregates' rather than single constructions and characterised by a structural behaviour depending on the mutual interaction of different structural units. An accurate knowledge process can allow the determination of structural units within the complex: such units can be therefore analysed using a specific evaluation form conceived to provide a 'risk ranking' of the different portions constituting the aggregate and accounting for vulnerability, exposure and seismic hazard parameters. The proposed methodology exploits what is already used to quickly determine structural features and eventual damages in the post-earthquake phase for ordinary buildings, introducing specific aspects typical of historical-cultural heritage requiring attention. According to the results achieved, retrofit interventions or deepen investigations can be planned for units provided by a higher position in the risk scale, optimising and rationally planning the use of available economic and time resources. In the present work, the proposed methodology is applied to the monumental complex of the Certosa di Calci, Pisa (Italy).