Objectives:Firefighters have elevated cancer incidence and mortality rates. MicroRNAs play prominent roles in carcinogenesis, but have not been previously evaluated in firefighters.Methods:Blood from 52 incumbent and 45 new recruit nonsmoking firefighters was analyzed for microRNA expression, and the results adjusted for age, obesity, ethnicity, and multiple comparisons.Results:Nine microRNAs were identified with at least a 1.5-fold significant difference between groups. All six microRNAs with decreased expression in incumbent firefighters have been reported to have tumor suppressor activity or are associated with cancer survival, and two of the three microRNAs with increased expression in incumbent firefighters have activities consistent with cancer promotion, with the remaining microRNA associated with neurological disease.Conclusion:Incumbent firefighters showed differential microRNA expression compared with new recruits, providing potential mechanisms for increased cancer risk in firefighters.