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Thyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence. PATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States. PATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases. PATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs. • This study used high-quality data sources and rigorous calibration to develop, to our knowledge, the first cross-population microsimulation model to replicate thyroid cancer epidemiology in the United States over time. • This study demonstrated the use of a stakeholder advisory board comprising patients, providers, policymakers, and researchers in building an epidemiologic microsimulation model. • This study successfully explained the drastic increase in the incidence of thyroid cancer since the 1990s through modeling of changing diagnostic pathways over time. [ABSTRACT FROM AUTHOR]