Skin cancer is the most common neoplasm in Caucasians in the United States with a lifetime risk nearly equal to that of all other cancers combined (1). More than 800,000 people are expected to develop nonmelanoma skin cancer [basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)] this year in the United States (2). Sun exposure is the major environmental agent implicated in induction of nonmelanoma skin cancer (3). While sun exposure begins early in life, the average patient with nonmelanoma skin cancer is about 60 years old (1)(Fig. 1). The article by Jonason et al.(4) in a previous issue of the Proceedings provides a new insight into the link between sun exposure and nonmelanoma skin cancer and furnishes information about events occurring between the time of initial sun exposure and subsequent skin cancer years later. The multistage theory of carcinogenesis is based on experimental studies in rodents and has been proposed as a general model for environmental carcinogenesis (5)(Fig. 2). In the first stage—initiation—a carcinogen mutates a target gene. Initiation is followed by promotion, a process in visibly normal skin in which the single damaged cell expands to form a clone of damaged cells. These changes progress, leading to precancerous clinically abnormal skin and then to cancer. Many experimental studies have been designed to dissect the cellular and molecular mechanisms involved in this process. These studies involve investigations of DNA repair, eicosanoid and proteinase production, cytokine activation and immune suppression, and specific tumorsuppressor genes including patched and p53 (Fig. 2).