Lung cancer is still diagnosed at a late stage although novel diagnostic techniques are in use. However, as pharmacogenomics have evolved novel targeted therapies either with tyrosine kinase inhibitors or immunotherapy can be currently used as daily treatment. We present the case of a woman with anaplastic lymphoma-positive expression and programmed death-ligand 1 (PD-L1) 0% score upon diagnosis who underwent therapeutic surgery and represented PD-L1 90% expression, however, without anaplastic lymphoma kinase expression. Transformation of the tumor or new tumor is a question to be answered for this patient and possibly we should try and direct rebiopsies for this group of targeted therapy patients.