Background Basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC) are the most common non‐melanoma skin cancer (NMSC). SOX2 is a transcription factor that acts on various phases of embryonic development and its overexpression in many tumors has been reported. Aim This work aimed to evaluate the possible role of SOX2 in pathogenesis of non‐melanoma skin cancer through its immunohistochemical assessment in BCC and SCC compared to normal skin and correlating its expression with the established prognostic factors. Methods The investigated cases were 24 BCC, 21 SCC, and 26 normal skin specimens. Results SOX2 was not expressed in normal skin, but it was upregulated in SCC (85.7%) and BCC (66.7%), with a significant difference between malignant cases and normal skin (p < 0.001). However, SOX2 expression did not differ between SCC and BCC. SOX2 expression was associated with large‐sized tumors in all malignant cases (BCC plus SCC) (p = 0.02) and in SCC (p = 0.043) alone together with its liability to be expressed in advanced stage in SCC (p = 0.063). Conclusions SOX2 was over‐expressed in cutaneous SCC and BCC without a significant difference. SOX2 may enhance progression of NMSC manifested by its association with large tumor size and advanced stage.