The detailed characterization of several subambient solid state transitions occurring in the pharmaceutical ingredient Ciclopirox between −20 °C and −85 °C was performed by using a combination of DSC, cold-stage optical microscopy, vibrational spectroscopies, solid state NMR at controlled temperature, structural analyses by single crystal X-ray diffraction, and temperature-resolved X-ray powder diffraction. The global analysis of the available data reveals that the mechanisms of these reversible transitions involve a subtle compromise between phenomena related to molecular disorder, cooperative release of strains induced by cooling, and structural reorganization associated with topotactic changes in crystal lattice and symmetry. However, no major change in the main features of crystal packings is observed during the successive single crystal-to-single crystal transitions, which highlights the difficulty to classify such transitions in the frame of conventional theoretical frameworks. The successive therma...