This paper presents a study of the Milano Centrale railway station aimed at assessing the seismic vulnerability of the monumental building. The work was carried out on the occasion of a big project to refurbish the station, including both the restoration of certain areas of high artistic value and the improvement of functionality with the current railway services. The seismic analysis is focused on the monumental part of the building, including the Coaches Gallery, the Tickets Hall and the Head Gallery. The safety level of the structure was assessed on the basis of comprehensive historical investigation, survey, testing and finite element analysis. The issue of checking the seismic safety of a large number of members is addressed using a step-by-step verification strategy. The results of the study show that the overall safety level of the structure is acceptable, although some local structural deficiencies need to be handled with a proper strengthening design.