The death registries of the plague epidemic of 1630, stored at the Archivio di Stato of Milano, have been interrogated via the EVA film technology (ethyl vinyl acetate film studded with crushed strong anion and cation exchangers as well as C8 resins). The EVA diskettes have been left in contact with the lower right margins of 11 different pages pertaining to the peak months of the raging disease (June through end of September) for 60–90min and then the captured material, after elution and digestion, analysed by mass spectrometry. The main findings: 17 Yersiniaceae family proteins, 31 different human keratins, 22 unique mouse keratins, about 400 peptides from different bacterial strains, 58 human tissue proteins and 130 additional mouse and rat tissue proteins. In addition, >60 plant proteins (notably potato, corn, rice, carrot and chickpeas), likely representing the meagre meals of the scribes, contaminating the pages, were detected. The significance of these unique findings is amply illustrated in the body of the article. SignificanceArchivists, historians, librarians usually explore the texts of ancient and modern manuscript in order to extract the meaning of the writing and understand the mood, feelings, political, philosophical and/or religious ideas therein expressed by the authors. With the present EVA methodology (the only one, at present, able to access our Cultural Heritage without damaging or contaminating it) we interrogate, instead, the support, be it paper, parchment, wood panel, cloth, canvas and the like, in order to extract invisible data, such as the presence of drugs, medicaments, infectious pathogens, human and environmental contaminants. Metabolites, proteins and peptides thus captured are then analysed via mass spectrometry. The unique data mined by this technology should considerably enlarge the (so far) restricted horizon of the writing exploration and add new insight on the environmental conditions in which such documents were produced as well as, importantly, on the health/pathological conditions of the authors. It is believed that the present technology, as here reported, will become the officially accepted one for exploring the world Cultural Heritage.