Aiming at the development of strategies to prevent the hand-foot-syndrome, we propose to evaluate the amount of chemotherapeutics in the human skin together with carotenoids the latter serving as marker substances for the dermal antioxidative status. This approach is demonstrated by applying two-color Raman spectroscopy at 785 and 532 nm excitation for selective detection of chemotherapeutics and carotenoids, respectively. Porcine ear skin has proven to be suited as a model for corresponding spectroscopic basic in-vitro investigations. (© 2011 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) (© 2011 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA)