Introduction. Thyroid cancer (TC) is the the most common malignant disease of the endocrine system. The incidence of the TC has been increasing worldwide, especially in female population. However, mortality from TC is low in both males and females. The objective of the paper was to determine and analyze incidence and mortality trends of TC in males and females in the central Serbia in the period 1999-2014. Method. Descriptive study was used. Data were obtained from the Serbian Cancer Registry. Crude and age-adjusted rates (ASR) of incidence and mortality were calculated. Trend and annual percentage change (APC) of the incidence and mortality rate with corresponding 95% confidence intervals (CI) were calculated by performing Jointpoint regression analyses. Results. A total number of new cases of TC was 3113. TC was diagnosed in 2343 females and 770 males (female-to-male ratio, 3 to 1). A total number of fatal cases was 770 (while 504 female and 266 male died from TC, female-to-male ratio, 2 to 1). TC was not common before 30 years of age. The highest incidence was recorded both in males and females aged 50-59. Joinpoint regression analysis showed the statistically significant increase of ASR of TC incidence in males in 1999-2014 period with APC of 6.2% (95%CI:4.2-8.3, p<0.001) and there was also significant increase of ASR of TC incidence in females in the same study period with APC of 6.1% (95%CI: 4.2-8.0, p<0.001). Joinpoint regression analysis showed an insignificant increase of ASR of TC mortality in males with APC of 2.4% (95%CI:-0.5-5.5, p=0.1). There was an insignificant decrease of ASR of TC mortality in females with APC of -1.3% (95%CI: -4.4-1.9, p=0.4). Conclusion. The increasing trend of age-adjusted incidence rate of TC both in males and females and decreasing trend of age-adjusted mortality rates of TC in during the period were registered. Females had higher age-adjusted incidence and mortality rates than males. Female to male ratio of incidence was 3:1 and for mortality 2:1. Measures of primary and secondary prevention are needed.