Background: Lung cancer is the leading cause of cancer related death worldwide. Molecular targeted therapies are routinely used for pulmonary adenocarcinomas, harboring therapeutically tractable genomic aberrations such as EGFR mutations, ALK and ROS1 fusions. Comparable therapeutic options are still missing for squamous and small-cell lung cancer. Results: Molecular analyses revealed a significant amplification of FGFR1 in 20% of squamous and 6% of small-cell carcinomas. Preclinical and first clinical trials with FGFR inhibitors have shown that this genomic alteration is therapeutically actionable. For detection of FGFR1 amplification fluorescence in situ hybridization is a specific biomarker assay. We review evaluation strategy and criteria for FGFR1 positivity. Conclusion: FGFR1 amplification represents a promising potential target in squamous and small-cell lung cancer.