The treatment strategy of differentiating lung carcinomas into small-cell lung carcinoma and non-small-cell lung carcinoma has been satisfactory until recently. The introduction of novel cytotoxic agents that affect a patient's response to therapy has made further differentiation important. Non-small-cell carcinoma represents a heterogeneous group of cancers with varying histologic subtypes, hence the necessity to subgroup them. In the case of adenocarcinoma and squamous cell cancer, their different responses to novel therapeutic agents and their higher occurrence make differentiation between them even more important. New markers such as desmoglein-3 (positive for squamous carcinoma) and Napsin A (positive for adenocarcinoma), which show improved specificity and sensitivity, may be particularly useful for this type of differentiation. In our study, 124 surgically resected specimens were used: 57 adenocarcinoma, 42 squamous cell carcinoma, 16 large-cell carcinoma, 1 small-cell carcinoma, and 8 typical carcinoid tumor samples. The sensitivity to desmoglein-3 and Napsin A was 92.8% and 85.9%, whereas specificity was 100% and 97%, respectively. The use of a desmoglein-3 and Napsin A double-staining strategy in our study confirmed that these markers are useful in differentiating pulmonary squamous cell carcinoma and pulmonary adenocarcinoma from other subtypes.