X-ray diffraction (XRD) complemented by Raman spectroscopy analyses of synthetic organic pigments in powder samples, layered paint systems, and commercial artists’ paints bound in acrylic, alkyd, and oil media are presented. The potential and limitations of the techniques to identify and characterize mixtures of these pigments, along with inorganic extenders, in works of art are exemplified and discussed. Stratified model paint systems that mimic the layering structure typically found in modern paintings are used to evaluate the effect of the [mu]XRD experimental parameters, as well as extenders or fillers commonly found in modern artists’ paint formulations, on the quality of the patterns recorded in micro-samples of paint. XRD is demonstrated for the first time to be an effective tool for the specific identification of synthetic organic pigments mixtures and fillers in acrylic and alkyd bound artists’ paints, while the identification of these pigments by XRD in oil paints appears problematic. Detailed crystallographic information provided by XRD is shown to be complementary to molecular information provided by Raman analysis. The combined use of these techniques allows for more frequent unambiguous compound identification than would be possible using one technique alone.