There has been a growing interest since the mid-1990s in the use of lasers as an alternative method of cleaning of painted surfaces to surpass the possible problems of irreversible modification caused by chemical or mechanical methods. The objective of this research is to extend the current understanding of excimer laser-induced discoloration effects on pigments mixed in oil medium. The study focuses on the response of samples of pure pigments and their mixtures widely used by painters in the nineteenth century, to different laser parameters. Characterisation of physical changes was performed using optical microscopy, colorimetry, scanning electron microscopy, and atomic force microscopy. It has been found that materials have different sensitivity to irradiation at 248 nm and that even if an ultraviolet wavelength is used, the photo-chemical mechanism may not be the predominant effect. The effect of irradiation on a pigment mixture cannot be predicted from the effect of the irradiation on the individual pigments.