Skin cancer is one of the most important type of cancers in the world. In this way, molecular investigation in order to detect some novel mechanisms and polymorphisms involved in cancer development can be impressive and vital. In this way, the aim of this study was the histopathological investigation of skin cancer and its relationship with polymorphism of CDKN2A gene. This case-control study was conducted in north of Iran and 36 samples of squamous cell carcinoma (SCC), 64 cases of basal cells carcinoma (BCC)  and 50 healthy control samples were investigated. Histopathological and tissue structures were evaluated after hematoxylin and eosin staining, under light microscope. In addition, investigating the CDKN2A gene polymorphism was carried out by using PCR_sequencing. 58% of patients were male. The mean age of patients was 63.69 years and the average tumor size was 3.57 mm. No CDKN2A gene polymorphism was observed in intron 1. The investigation of other DNA repair genes can help to better understanding of genetic factors predisposing to skin cancer development.