BACKGROUND: The relationship between physical activity and risk of cutaneous squamous cell carcinoma (SCC) is unknown and difficult to investigate due to confounding by sun exposure. We prospectively examined the association of recreational and occupational physical activity and incidence of SCC accounting for photoaging and other risk factors. METHODS: We used available information on physical activity from the Australian population-based Nambour Skin Cancer Study comprising 1,171 adults aged 25-75 years at baseline (1992). In sex-stratified analyses (person-based and tumor-based) we estimated the associations between type of activity and incidence of SCC prospectively to 2007. RESULTS: During 16 years of follow-up, 98 men and 90 women newly developed SCC. We found no significant association between recreational activity measures and SCC after controlling for potential confounding factors including indicators of sun exposure. In men, the observed risk pattern was however suggestive of elevated risk with increasing total hours of recreational activity (compared to inactive men, RR (95%CI) 0.89 (0.54, 1.46) for less than or equal to 1.5 hrs/wk; 1.29 (0.82, 2.04) for less than or equal to 4.0 hrs/wk; 1.33 (0.86, 2.05)for more than 4.0 hrs/wk), while among women, higher level of occupational activity (standing and manual versus sedentary work activities) was associated with a reduced incidence of SCC tumors (P trend=0.03). CONCLUSIONS: Despite some suggestion that recreational activity in men and occupational activity in women are related to occurrence of SCC, there is no firm support for a role of physical activity in the development of cutaneous SCC.