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[en] There is increased need for classification of non-small cell lung cancer (NSCLC) into its major subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC). Such a classification is enabled in poorly differentiated tumours based on routine morphology due to overlapping morpho- logic features. In such cases, the use of immunohistochemistry (IHC) can differentiate between the two subtypes. Purpose: To test the ability of the two markers; Napsin-A and Desmocollin-3, in differentiating poorly differentiated (AC) from poorly differentiated SCC in small biopsies. Patients and methods: This is a retrospective study including 60 patients who presented with pulmonary nodules. Cases with biopsy specimens diagnosed as poorly differentiated non-small cell lung cancer, and had corresponding resection specimens were included. Cell blocks were stained with anti Napsin-A, and anti Desmocollin-3. Cytoplasmic immunoreactivity for both markers was considered specific. Sensitivity, specificity, positive and negative predictive values, total accuracy and combined accuracy of both markers were calculated. Results: Napsin A showed a sensitivity of 89.3%, a specificity of 96.9%, PPV of 96.2%, NPV of 91.2%, and a total accuracy of 93.3% for AC, while Desmocollin-3 achieved 90.6% sensitivity, 96.4% specificity, 96.7% PPV, 90% NPV, and 93.3% total accuracy. Both markers achieved a total accuracy of 90%. Conclusion: Napsin-A, and Desmocollin-3 were sensitive and specific markers for the diagnosis of AC and SCC, respectively. Both markers allowed classification of 54/60 cases into either AC or SCC.