Very few previous studies have examined the relationship between thyroid cancer risk and intake of phytoestrogens (PE); furthermore, these studies have reached inconsistent results. We analyzed data from a population-based case-control study in Connecticut from 2010 to 2011, including 387 histologically confirmed thyroid cancer cases and 433 population-based controls, with compound data available concerning specific PEs. Multivariate unconditional logistic regression models were used to estimate the associations between specific PEs and the risk of thyroid cancer, adjusting for potential confounders. An elevated risk of thyroid cancer was associated with moderate to high levels of coumestrol intake [OR = 2.48, 95% confidence interval (CI), 1.39-4.43 for 40-80 μg/day; OR = 2.41, 95% CI, 1.32-4.40 for 80-130 μg/day; and OR = 2.38, 95% CI, 1.26-4.50 for >200 μg/day compared with <40 μg/day], and the main elevation in risk appeared among microcarcinomas (≤1 cm). A decreased risk of papillary macrocarcinomas (>1 cm; OR = 0.26, 95% CI, 0.08-0.85 for 1,860-3,110 μg/day compared with <760 μg/day) was associated with moderate genistein intake among women. Our study suggests that high coumestrol intake increases the risk of thyroid cancer, especially microcarcinomas, whereas moderate amounts of genistein intake appear to be protective for females with thyroid macrocarcinomas. The study highlights the importance of distinguishing between microcarcinomas and macrocarcinomas in future research on the etiology of thyroid cancer. ©2019 American Association for Cancer Research.