BACKGROUND: The global population aged 80 years or older is expected to triple by 2050, leading to an increased cancer burden in the oldest population. This study describes the estimated cancer incidence and mortality in 2022 and projections for 2050 in the oldest old, analyzed globally and by world regions and World Bank income levels, for all sexes combined, as well as separately for males and females. METHODS: Using GLOBOCAN 2022 estimates, we reported the estimated number of new cancer cases (excluding non-melanoma skin cancers), deaths, and truncated age-standardized incidence (ASIR) and mortality rates (ASMR) (per 100,000 individuals aged 80 years or older). We also presented the top five cancers by cases and deaths. Additionally, we projected the number of new cancer cases and deaths for each region in 2050, assuming no change in cancer incidence and death rates. RESULT: In 2022, an estimated 2.6 million new cancer cases (14 % of all cancer cases) and 2.1 million cancer deaths (22 % of all cancer deaths) occurred in the oldest old, with regional variations. Globally, lung, colorectal, and prostate cancers were the most common cancers diagnosed and leading causes of cancer death. ASIR ranged from 987 in Africa to 2044 per 100,000 in Northern America while ASMR ranged from 981 in Africa to 1769 per 100,000 in Oceania. In 2050, an estimated 7.4 million new cancer cases and 6 million cancer deaths are expected. The greatest increases are anticipated in China, India, and Africa, with increases exceeding 200 % compared to 2022 estimates. CONCLUSION: The growing cancer burden among the oldest old poses significant challenges to global healthcare systems, necessitating resource-tailored adaptations. These findings call for the inclusion of the oldest old in the development and implementation of cancer control policies and a better representation in cancer research.