Increase of targeted anticancer therapies led to the beginning of a new era of cancer treatment, partly instead of classical chemotherapies, partly supplementing these.While for a number of substances only clinical experiences are relevant for treatment decisions, for some major cancer groups predictive markers are known indicating probably tumor responses.Modem techniques used for the pathological diagnosis tries to identify the latter.Therefore a need for companion diagnostics is given, sometimes existing as pretherapeutic immunohistochemical or genetic testing.The most important and successful antibody therapies of solid tumors cover the EGFR/Her-2/neu group.A real breakthrough in targeted cancer therapies could be reached by use of trastuzumab in Her-2/neu overexpressing breast cancer due to Her-2/neu gene amplifications.Since last year these therapies are known to be successful in a subset of gastric carcinomas too.During the last few years we learned about the impact of K-ras wild type in colorectal carcinomas to predict response to cetuximab (anti-EGFR).Furthermore, in advanced stages of NSCLC subgroups, the importance of activating EGFR mutations was found as marker ofgood tumor response to gefitinib, but also erlotinib (both tyrosine kinase inhibitors).In some countries these settings are already approved as first line therapies for advanced stages and metastasizing tumors.This presentation focuses on the use of classical and novel diagnostic techniques in modern pathology important for personalized anti-cancer medicine, reporting recent advances in identifying and characterizing tumor subgroups responding to targeted therapies.On one hand patients are gaining major advantages due to more personalized and better tolerable cancer treatment, on the other hand these developments enable cost intensive targeted drug investigations and trials especially in a situation of limited health care budgets.