The varied effects of different classes of dietary fatty acids on carcinogenesis suggest that fatty acid composition is an important determining factor in tumor development. In the present study, we investigated the association between dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the skin (SCC). Data were taken from a population-based case-control study of skin SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95% confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74 (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies are clearly needed to elucidate the function of dietary fatty acids so that recommendations can be made to alter the human diet for cancer prevention, particularly in light of the increasing incidence of SCC of the skin.