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Flight attendants may have elevated breast cancer incidence (BCI). We evaluated BCI's association with cosmic radiation dose and circadian rhythm disruption among 6,093 female former U.S. flight attendants.We collected questionnaire data on BCI and risk factors for breast cancer from 2002–2005. We conducted analyses to evaluate (i) BCI in the cohort compared to the U.S. population; and (ii) exposure-response relations. We applied an indirect adjustment to estimate whether parity and age at first birth (AFB) differences between the cohort and U.S. population could explain BCI that differed from expectation.BCI was elevated but may be explained by lower parity and older AFB in the cohort than among U.S. women. BCI was not associated with exposure metrics in the cohort overall. Significant positive associations with both were observed only among women with parity of three or more.Future cohort analyses may be informative on the role of these occupational exposures and non-occupational risk factors. Am. J. Ind. Med. 58:252–266, 2015. © 2015 Wiley Periodicals, Inc.