: Flight crew are occupationally exposed to several potentially carcinogenic hazards but previous investigations have been hampered by lack of information on lifestyle exposures. The authors identified, through the United Kingdom Civil Aviation Authority medical records, a cohort of 16,329 flight crew and 3,165 air traffic control officers (ATCOs) and assembled data on their occupational and lifestyle exposures. Standardized incidence ratios (SIRs) were estimated to compare cancer incidence in each occupation to that of the general population; internal analyses were conducted by fitting Cox regression models. All-cancer incidence was 20-29% lower in each occupation than in the general population, mainly due to a lower incidence of smoking-related cancers (SIR (95% CI): 0.33 (0.27, 0.38) and 0.42 (0.28, 0.60) for flight crew and ATCOs, respectively), consistent with their much lower prevalence of smoking. Skin melanoma rates were increased in both flight crew (SIR=1.87; 95% CI: 1.45, 2.38) and ATCOs (2.66; 1.55, 4.25), with rates among the former increasing with increasing number of flight hours (P-trend=0.02). However, internal analyses revealed no differences in skin melanoma rates between flight crew and ATCOs (hazard ratio: 0.78, 95% CI 0.37, 1.66) and identified skin that burns easily when exposed to sunlight (P=0.001) and sunbathing to get a tan (P=0.07) as the strongest risk predictors of skin melanoma in both occupations. The similar site-specific cancer risks between the two occupational groups argue against risks among flight crew being driven by occupation-specific exposures. The skin melanoma excess reflects sun-related behaviour rather than cosmic radiation exposure. © 2012 Wiley-Liss, Inc.