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Background The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. Methods A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996–2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. Results In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996–2000 (95% confidence interval [95% CI]: 2.2–2.6) to 7.5 per 100,000 during 2011–2015 (95% CI: 7.3–7.9), corresponded to an overall APC of 8.7 (95% CI 7.6–9.9). The APC in men and women was 6.2 (95% CI: 4.2–8.2) and 9.2 (95% CI: 8.0–10.4), respectively. The incidence rate in the Conclusions There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.