e20048 Background: Lung and bronchus cancer incidence rates have been reported to be higher among females than males under the age of 50, particularly after 2004. The first e-cigarette device emerged in 2003, raising questions about its potential impact on cancer incidence in females compared to males and its connection to the sudden rise in female cases. This study aims to investigate sex differences in cancer incidence across diverse racial and ethnic groups, aiming to determine whether these variations stem from biological factors or unexplored environmental exposures. Methods: Cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) program (2000-2020) were utilized to analyze female-to-male incidence rate ratios (FM IRR) for young-onset lung and bronchus cancer diagnosed before the age of 50. The data was stratified by race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic) and age-standardized to the 2000 U.S. population. Results: In the period from 2000 to 2020, 41,066 patients with lung and bronchus cancer under the age of 50 were identified. Incidence trends showed a consistent decrease each year, reaching the lowest rates in 2020 (2.1 per 100,000 cases) and the highest in 2000 (4.9 per 100,000 cases). Males accounted for 49.4% (20,303), while females constituted 50.6% (20,763). Despite the overall declining trend, FM IRR steadily increased post-2004, exhibiting a constant rise between 2005 and 2020. Non-Hispanic White comprised 65.9% of the cases, with the second and third largest groups being Non-Hispanic Black (15.3%) and Hispanic (9.62%). Incidence rates were highest among non-Hispanic Black (4.9 per 100,000 cases), followed by non-Hispanic White (4.2 per 100,000 cases), and lowest in the Hispanic population (1.6 per 100,000 cases). Young-onset lung and bronchus cancer diagnosed before age 50 showed a female predominance after 2004, with the Hispanic population having the highest FM IRR between 2000 and 2020 (1.13), followed by Non-Hispanic American Indian/Alaska Native (1.09) and Non-Hispanic White (1.02). There was a lower FM IRR among Non-Hispanic Black and Non-Hispanic Asian/Pacific Islander (0.83) and (0.96), respectively. Conclusions: The FM IRR for young-onset lung and bronchus cancer exhibited variations among racial and ethnic groups, with the highest rates observed among the Hispanic population. This study was limited by the absence of data on smoking habits and other environmental factors. Further research is needed to investigate the influence of e-cigarettes and other environmental factors on the incidence of lung and bronchus cancer, considering variations by sex.