Non-melanoma skin cancer is common and offers unrivaled opportunities to relate genetic changes to clinical and biologic behavior. Recent technical advances in molecular biology render genetic analysis of even the smallest skin cancers possible. In this review I will discuss the role of p53 gene in skin carcinogenesis, the relation between p53 immunostaining and p53 mutation, and recent evidence for the involvement of putative tumor suppressor genes both on chromosome 9 and other chromosomes in non-melanoma skin cancer.