Could not be possible that rock paintings with similar hues and morphologies were the result of different paint preparations inside a cave but distanced in time? Is there any archaeometric approach that allow us to evidence these subtle differences? Aiming to address these inquires, in this work are presented the potentials of new physicochemical lines of evidence for characterization and differentiation of paint mixtures. This will improve the understanding of the technical heterogeneity and temporal complexity of painting sets executed in a particular archaeological site. In order to explore these points, the results obtained in the micro-stratigraphic studies of samples taken from the painted walls of Oyola, an archaeological site located in the northwest of Argentina, are presented. These samples have been analyzed by micro-Raman spectroscopy (mRS) and scanning electron microscopy with energy dispersive X-ray (SEM-EDS). The differences found by cross-section chemical studies could be explained as a consequence of two situations: 1- differences in the painting’s chemical components, either in the pigments involved or additives used; and, 2- differences in the physical properties of the mixtures such as stratum thickness and/or particle size. Also, in this article are explained each of the hypothesis, presenting the limits of these interpretations and pointing out future research challenges. As we discussed, it could be possible that the chemical and physical differences found between paint mixtures were the material expression of varied types of pictorial techniques.