In this book chapter we report our own experience of mutational analysis in selecting tailored anticancer treatments for solid tumors. Our Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy, routinely performs pharmacogenetic screenings for different genes such as K-ras, BRAF, KIT, PDGFRα, and EGFR on paraffin-embedded cancer sections. Therefore, the chapter describes the mutational analysis procedures on paraffin-embedded tumors aimed to predict individual response to anticancer therapy. These molecular diagnostic methodologies may help us in improving the translational impact of genetic information on clinical practice.