Aim To compare occupational flying hours (a surrogate for occupational exposure to radiation) of commercial pilots subsequently diagnosed with melanoma, with those without melanoma. Methods Nested case-control study of de-identified male commercial pilots in Australia 2011-2016, ascertained through the Civil Aviation Safety Authority (CASA). Cases were pilots diagnosed with melanoma 2011-2016; controls were randomly-selected pilots age-matched 1:2 with invasive cases. Total flying hours and hours flown in the last 6 months in 2011, date of birth and state of residence were also obtained. We estimated the association between total flying hours (in tertile groups), and melanoma by odds ratios adjusted for age and state (ORsadj; 95% confidence intervals (CIs)). Results During 2011-2016, 51 pilots developed invasive melanoma and 63, in situ (mean ages 47 and 49 years, respectively). Their median cumulative flying hours in 2011 were 6,108 and 6,900 respectively, compared with 7,500 for 102 control pilots (mean age 48.6). Risk of invasive melanoma did not increase per 1000 total hours flown (ORadj=1.00) nor did risk increase in pilots with highest vs lowest total flying hours (ORadj=1.18, 95% CI 0.44-3.15). Total flying hours were inversely associated with invasive melanoma development in pilots aged < 50 (ORadj=0.37, not significant), and not associated with melanoma on exposed sites. Recent flying hours were not associated with melanoma. Results were unchanged with inclusion of in situ cases. Conclusion Risk of melanoma in Australian commercial pilots is unrelated to cumulative or recent occupational exposure to radiation as indicated by total and recent flying hours.