Non-Keratinizing Squamous Cell Carcinoma (SCC) vs Solid-predominant Adenocarcinoma of Lung: Some solid adenocarcinomas of lung have dense eosinophilic cytoplasm and closely resemble SCC. Immunohistochemically, adenocarcinomas are positive for TTF1 and Napsin A and negative for squamous markers such as p40 and p63. Centrally-located Well-differentiated SCC with a Papillary Endobronchial Component vs Squamous Papilloma: Demonstration of unequivocal invasion supports the diagnosis of SCC. SCC of Lung vs Metastatic Urothelial Carcinoma: Both tumors can be positive for p40, p63, and CK7; however, urothelial carcinoma is also generally positive for GATA3, uroplakin III, and CK20. SCC of Lung vs Thymic Squamous Cell Carcinoma: Distinction on histopathologic findings may be difficult and require correlation with operative and radiologic findings. Primary SCC of Lung vs Metastases (Head & Neck, Esophagus, Cervix): Occasionally, a patient with SCC in lung has a prior history of squamous cell carcinoma at another location. In such circumstances, correlation of TP53 mutation status, p53 immunohistochemical profile, loss of heterozygosity involving microsatellite markers, HPV status, and p16 immunohistochemistry between lung tumor and the primary tumor from other location becomes important.