lntroduction: The main difference between two closely related entities, keratoacanthoma and squamous cell carcinoma is a spontaneous regression displayed by KA. lt has been suggested that apoptosis plays a part in process of KA involution, although exact trigger and mechanisms remain unclear. A tumor progression is often seen in the presence of substantial lymphocytic infiltration, suggesting that these T cells are not capable of mounting an effective immune response to control tumor growth. Studies suggested that the tumor regression depends mainly on the i mm une response mediated by cytotoxic T lymphocytes (CD8+) supported by helper T cells (CD4+). Cytotoxic T cells can kill tumor cells and mediate tumor regression through binding of death ligands and receptors, and by direct exocytosis of granules containing granzyme B, considered a main executor of anti-tumor response. Aims: To elucidate a possible roll of pro-apoptotic and anti-apoptotic proteins, cytotoxic T cells and granzyme B expression in keratoacanthoma regression and squamous cell carcinoma progression. Materials and methods: 150 samples, 30 samples of each, normal skin, keratoacanthoma (proliferative and regressing) and squamous cell carinoma (well differentiated and poorly differentiated) were analyzed immunohistochemically for expression of p53, Ki-67, bak and bcl-2 proteins, as well as CD3, CD8, CD4 and granzyme B. Results: Significant increase in p53 and Ki-67 proteins expression was observed in all tumor lesions examined in comparison to normal skin. There was an increase of the bak protein expression in keratoacanthomas as compared to norma! skin. Contrary, we have detected a significant reduction of bak protein expression in poorly differentiated squamous cell carcinomas as compared to norma! skin and proliferative keratoacanthoma. Bcl-2 protein expression was similar in normal skin and squamous cell carcinomas, but there was a decrease in regressing keratoacanthoma. A significantly higher number of granzyme B positive cells was detected in proliferative and especially regressing keratoacanthoma as compared to poorly differentiated quamous cell carcinoma. The tumors were variably infiltrated with CD3+, CD8+ and CD4+ T cells but the density of the infiltrate was significantly higher as compared to normal skin (p<0,0001). The highest intensity of CD3+, CD8+ and CD4+ T cells infiltrate has been found in regressing keratoacanthomas. Granzyme B expression was significantly increased in all tumors as compared with normal skin (p<0,0001). Expression of this cytotoxic protein was significantly increased in regressing (p<0,0001) and proliferative keratoacanthomas (p=0,042) as compared to poorty differentiated squamous cell carcinomas. Conclusions: Decreased bcl-2 expression in conjunction with increased bak expression in regressing keratoacanthoma could play a role in its regression. Contrary to that finding, a steady level of bcl-2 protein in poorly differentiated squamous cell carcinoma, combined with decreased bak levels and high proliferation rate could contribute to progression and aggressiveness of these tumors. ln our opinion, inadequate immune response characterized by lower inflammatory infiltrate and insufficient secretion and/or activity of granzyme B could contribute to squamous cell carcinoma progression as opposed to keratoacanthoma regression. This study demonstrates significant differences in activation state of tumor infiltrating lymphocytes in examined skin tumors.