Summary Generally, the cumulative UV exposure correlates with the site-specific incidence of skin cancer but more detailed analysis showed that the frequency of BCC of some facial regions cannot be explained with site-specific UV exposure. Apoptosis plays a central role in cancer development due to suppressed process of programmed cell death. Anatomic localization, UV and senescence can influence expression of apoptosis related molecules resulting in advantage of cancer cells development and tumor progression. Anti-tumor immune response, as an important factor in elimination of cancer cells, is also modified by UV radiation and aging, further contributing to cancer progression and its development. Hypothesis : UV radiation, senescence and proliferation intensity influence the expression of apoptosis related molecules in normal keratinocytes. Mutated cells express altered molecules with different degree of antigenicity. We propose that small differences in the expression of pro- and anti-apoptotic molecules in the keratinocytes in association with the local immune reaction (modulated also by UV radiation) determine the type of the non-melanoma skin cancer as well as their frequency (site-specific incidence). In vitro and in vivo models could explain how the modulation of UV can influence the apoptotic system and local immune reaction, while animal experiments could explain different site-specific incidence (frequency) of the same tumor. Better understanding of these mechanisms could lead to development of different therapeutic approaches for early elimination of cancer prone cells or cells in early stages of cancer development. The same model could be used to explain the site-specific localization of other types of cancer (i.e. melanoma) or benign tumors.