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Lung cancer high mortality rate remains a major problem, despite the actual progress in its early detection and therapeutic design. Since lung cancer' treatment requires separation of tumors in small cell carcinoma and non-small cell carcinoma, the histopathological diagnosis focuses on this basic distinction, while immunohistochemistry contributes considerably to confirm the diagnosis accuracy. In order to check the assumption that p63 is a useful marker for squamous cellular differentiation, we used two antibodies: anti-p63 and anti-thyroid transcription factor-1 (TTF-1), based on their immunoexpression to differentiate small cell lung carcinoma (SCLC) from poorly differentiated nonkeratinizing squamous cell carcinoma (SCC). Our study included 48 cases of lung carcinoma (lung biopsies and wedge resection formalin-fixed and paraffin-embedded). The 48 cases included 23 SCLCs and 25 poorly differentiated nonkeratinizing SCC. The expressions of p63 and TTF-1, respectively, proved to be useful in distinguishing SCLC from poorly differentiated nonkeratinizing SCC, on surgical and biopsic sections. The p63 positivity and TTF-1 negative expression consequently indicated a poorly differentiated nonkeratinizing SCC, while the opposite immunostaining pattern was flagged in SCLC. Our results are useful for a targeted therapy, as long as they point out a significant role in marking of the correct diagnosis of lung tumors.