Abstract Background: The global increase of the incidence of early-onset cancers (defined as cancers diagnosed at 20-49 years) is a serious public health problem. However, it is understudied whether the incidence of early-onset cancers has increased in parallel with that of later-onset cancers (defined as cancers diagnosed at 50 years or above) or only the incidence of early-onset cancer has increased worldwide. We therefore evaluated the recent global trends of the incidence of early-onset cancers and later-onset cancers. Method: We retrieved sex-stratified age-standardized incidence rates of early-onset cancer and later-onset cancer diagnosed between 2000 and 2012 in 39 countries where data was available from the GLOBOCAN database. Using joinpoint regression models, we assessed average annual percentage change (AAPC) by cancer types and countries, with statistical significance corresponding to a 95% CI that does not include zero. Results: We observed statistically significant positive AAPCs for early-onset cancers (AAPC [95% CI], 1.9% [1.8%, 2.1%] for females, 0.7% [0.6%, 0.9%] for males in all available countries combined) in many early-onset cancer types, including colorectal, esophagus, gallbladder, kidney, liver, multiple myeloma, pancreas, prostate, stomach, testis, thyroid and uterine cancer in many parts of the world. There were variations in many later-onset cancer types depending on cancer types and countries. Notable cancer types that have significantly increased in early-onset cancers but have decreased or showed no change in later-onset cancers include colorectal (5 countries in females and 6 countries in males), uterine (4 countries), and thyroid cancers (5 countries in females and 3 countries in males). In particular, early-onset colorectal cancer has increased but later-onset colorectal cancer has decreased among both sexes in Canada (AAPC [95%CI], early-onset: 1.6% [0.9%, 2.7%], later-onset: -0.8% [-1.0%, -0.5%] for females; early-onset: 1.8% [1.0%, 2.6%], later-onset: -1.2% [-1.5%, -0.9%] for males), USA (Early-onset: 2.0% [1.5%, 2.5%], later-onset: -2.7% [-2.9%, -2.6%] for females; early-onset: 1.6% [1.1%, 2.2%], later-onset: -3.2% [-3.7%, -2.6%] for males), Australia (Early-onset: 1.8% [0.7%, 2.9%], later-onset: -1.0% [-1.5%, -0.6%] for females; early-onset: 1.4% [0.7%, 2.4%], later-onset: -1.5% [-1.9%, -0.9%] for males). Conclusion: Our study highlights differences in cancer incidence trends between certain early-onset and later-onset cancer types in many parts of the world. Notably, early-onset colorectal, uterine, and thyroid cancers have significantly increased but corresponding later-onset cancers have decreased or showed no change in many countries. Different patterns in cancer incidence trends of early-onset and later-onset cancers in different regions should be further investigated to better understand and prevent the increase in the incidence of early-onset cancers. Citation Format: Miyu Terashima, Hwa-Young Lee, Yuta Tsukumo, Satoko Ugai, Minkyo Song, Naoko Sasamoto, Ichiro Kawachi, Tomotaka Ugai. Diverging global incidence trends of early-onset and later-onset cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4847.