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Background: Little epidemiologic research has focused on the role of immune function in papillary thyroid cancer risk despite scattered observations suggesting it may be important (e.g., hygiene hypothesis). Here we investigate papillary thyroid cancer risk associated with self-reported living environments across the lifespan reflecting immunologically relevant exposures to microbial-rich environments., Methods: Among 61,803 eligible participants in the California Teachers Study cohort, 100 were diagnosed with invasive papillary thyroid cancer between 2005 and 2012. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI)., Results: Living in a rural area during early childhood was associated with significantly reduced risk of developing papillary thyroid cancer as an adult (HR=0.51, 95% CI: 0.28-0.94). Specifically, reduced risks were observed for living within a half mile of hoofed animals (HR=0.47, 95% CI: 0.26-0.84), as was having an indoor dog or cat (HR=0.51, 95% CI: 0.32-0.80). Neither sharing a bedroom or living in a rented home as a child nor attending daycare or kindergarten was associated with reduced risk., Conclusions: Early childhood exposures to hoofed animals or indoor furry pets were associated with reduced risk of subsequently developing papillary thyroid cancer., Impact: Our findings point to immunologically relevant, early-life exposures to microbial-rich environments as potentially important in reducing thyroid cancer risk, consistent with the hygiene hypothesis and suggesting that certain, possibly animal-derived, microbial exposures may be important to immune calibration or priming., (Copyright © 2015 Elsevier Ltd. All rights reserved.)