text: BACKGROUND: Although tobacco smoking is commonly cited as a risk factor for cutaneous squamous cell carcinoma (SCC), the evidence from previous clinical and case-control studies is conflicting. We therefore aimed to prospectively examine the role of tobacco smoking in the development of SCC of the skin in a population-based study. METHODS: Study participants were 1,287 adults aged 25 to 75 years in 1992, randomly selected from the Nambour community, with no previous history of SCC. Standard skin pigment and sun-sensitivity profiles were obtained at baseline. Detailed prospective information on sun exposure, smoking, and skin cancer occurrence (histologically confirmed) was collected over a 16-year period, 1992 to 2007. RESULTS: Of 1,287 participants, 43% were male and average age was 48 years. A total of 188 first cutaneous SCCs were identified during the study period. After adjustment for other known risk factors, neither former nor current smokers were at raised risk of SCC: relative risk (RR) = 1.1, 95% CI: 0.8-1.5 and RR = 1.1, 95% CI: 0.7-1.5, respectively, compared with lifelong nonsmokers, nor were there any dose-response relationships with amount smoked or duration of smoking and risk of SCC. CONCLUSIONS: In this Australian follow-up study, tobacco smoking did not increase the risk of SCC of the skin. IMPACT: These prospective adjusted data provide strong evidence which suggests that cutaneous SCC should not be on the list of tobacco-related cancers.