The introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for non-small cell lung cancer (NSCLC) with activating mutations of the EGFR has opened a new area of lung cancer treatment strategies and led to an enthusiastic search for additional mutations. Since then, numerous driver mutations such as EML4-ALK and ROS1 have been detected and specific treatment options have already been developed. However, molecular tests have to follow specific rules if applied in daily practice. The Austrian Working Group on Pulmonary Pathology and Oncology (AWGPPO) is presenting an updated version of their previous recommendation published in 2011. Several practical questions raised during the last 2 years will be addressed, such as reflex testing, selection of tissues, order of molecular tests, and the issue of resistance mechanisms.