Variability has always been a key concept in the humanities, as a factor of change and historical evolution as well as the core phenomenon between normativity, social control and individuality. Variability in written cultures is an issue for communication and literacy studies, linguistics, philology, history and palaeography, but also psychology and neuroscience. In order to better understand the challenges presented by modern technology, the variability of medieval scripts is an excellent field of research. This article details how palaeography connects to the context and rationale to study the variability of scripts, and evidences how core features such as letter-forms can be analysed in relation to semiotic coherence, phonetics, linguistics and neuroscience. It suggests that variability would be precisely a question for “digital palaeography” to be addressed with the help of computer vision. In the last part, it describes the strategy that has been implemented within the research project ORIFLAMMS (Ontology Research, Image Feature, Letterform Analysis on Multilingual Medieval Scripts, 2013-2016) to created the necessary data sets and tools, especially to build a common reference corpus and a formal ontology which should serve as a touchstone to measure variability. The conclusion lists the achievements of the cross-domain research project, ranging from the reference corpus to new open source developments for text-image alignment and joint palaeographical and linguistic analysis, passing through new publications on digital humanities and interdisciplinary research.