Substituted N-salicylidene aniline has been quantitatively prepared by mechanochemical synthesis starting from the corresponding aniline and ortho-vanillin. X-ray diffraction reveals that the compound crystallizes into two different polymorphic forms, due to its conformational flexibility. Ab initio conformational calculations combined with a CSD survey allow proper definition of the conformational space and selection of specific starting geometries for crystal structure prediction studies. Therefore, theoretical packing simulation was able to retrieve the two polymorphic structures in agreement with the experimental data. DSC calorimetric analysis provides extra information on the thermodynamic relationship between polymorphs I and II, and their exposure to liquid nitrogen, coupled with low-temperature X-ray analysis, highlights the structural reasons for the intrinsic thermochromic behaviour of the compound.