Squamous cell carcinoma (SCC) represents the second most common histologic subtype of lung cancer (preceded only by adenocarcinoma). SSC of the lung is prevalently diagnosed in smokers and has been described as a preferentially centrally located tumor in which the main airways are commonly involved. Clinically, it presents with predominant locoregional signs and symptoms, but in recent years an increasing frequency of peripheral SCC of the lung has been reported. Pathologic diagnosis can be easily made through light microscopy and immunohistochemistry. The treatment approach for early-stage disease does not differ from that of other histologic subtypes of non-small cell lung cancer; in locally advanced unresectable or metastatic disease, doublet chemotherapy regimens (including cisplatin or carboplatin and a third-generation agent such as gemcitabine, taxanes, or vinorelbine) remain the cornerstone of front-line systemic treatment. Conversely, a single agent, mainly docetaxel, is the preferred treatment in second-line treatment. In unselected patient populations, targeted therapies have been extensively tested in combination with cytotoxic chemotherapy with disappointing results because of increased toxicity or lack of improvement in efficacy outcomes. Genomic alterations in SCC of the lung have not been comprehensively characterized, and no molecularly targeted therapies have been specifically developed for the treatment of this disease, but recently immune checkpoints have emerged as new therapeutic agent.