We present a completely non-destructive approach to analyse a set of historical glass mosaic tesserae. Aim of the study is to obtain a qualitative and quantitative characterization of the glass matrix in terms of elements and mineralogical phases. Several non-destructive techniques have been applied like Particle-Induced X-ray Emission, Particle-Induced Gamma-ray Emission, micro-Raman spectroscopy, neutron resonance capture analysis and neutron activation analysis in order to combine different technique strengths and to explore the effect of different range sizes for the analysis. Yet, best practices require the use of combined analysis and different skills. The paradigm of a non-destructive multi-analytical approach is suggested for a comprehensive investigation in non-homogeneous real samples, like historical glass mosaic tesserae.