ObjectivesCancer is an increasing cause of death and disability in Brazil and a pivotal vector for growing health expenditures. Lower levels of leisure-time physical activity are associated with a higher risk of some cancers. We quantified the current and future cancer direct healthcare costs attributable to insufficient leisure-time physical activity in Brazil.MethodsWe performed a macrosimulation model using: (i) relative risks from meta-analyses; (ii) prevalence data of insufficient leisure-time physical activity in adults ≥ 20 years; (iii) national registries of healthcare costs of adults ≥ 30 years with cancer. We used simple linear regression to predict cancer costs as a function of time. We calculated the potential impact fraction (PIF) considering the theoretical-minimum-risk exposure and other counterfactual scenarios of physical activity prevalence.ResultsWe projected that the costs of breast, endometrial, and colorectal cancers may increase from US$ 630 million in 2018 to US$ 1.1 billion in 2030 and US$ 1.5 billion in 2040. The costs of cancer attributable to insufficient leisure-time physical activity may increase from US$ 43 million in 2018 to US$ 64 million in 2030. Increasing leisure-time physical activity could potentially save US$ 3 million to US$ 8.9 million in 2040 by reducing the prevalence of insufficient leisure-time physical activity in 2030.ConclusionOur results may be helpful to guide cancer prevention policies and programs in Brazil.