Besides evidence- and guideline-based tumor therapy, personalized targeted therapies within study settings or individual experimental settings in advanced cancers without further therapeutic options are emerging. A comprehensive molecular analysis of the tumor in a molecular pathology laboratory is important for all targeted therapy approaches. However, the interpretation of the molecular results is crucial and potential therapeutic conclusions can only be drawn by considering the clinical situation and within a setting of oncological experience. Therefore, the molecular results and their potential impact have to be discussed at a molecular tumor board, an interdisciplinary expert team consisting of clinicians, oncologists, (molecular) pathologists, systems physicians, study teams and where required geneticists. If the molecular tumor board decides a targeted therapeutic approach is appropriate, patients should be enrolled in studies or registries with controlled settings and documentation in order to evaluate the therapeutic concepts. Furthermore, molecular-based individual experimental therapies are possible within extreme clinical situations.