Patients with Cushing's syndrome (CS) have higher risk of obesity and diabetes, which are important risk factors of cancers. However, if patients with CS have a higher incidence of cancer remains unknown. To investigate if endogenous CS is associated with increased cancer incidence. A nationwide cohort study. Analysis of the data retrieved from Taiwan's National Health Insurance program in 2006-2017. Between 2006-2017, 1278 patients with newly diagnosed endogenous CS were identified. Among them, 1246 patients without a history of malignancy were enrolled in this study. Endogenous CS. The age- and sex-standardized incidence rate of all-cause cancer and age-sex-calendar year standardized incidence ratio (SIR) of cancer in association with endogenous CS. The age- and sex-standardized incidences of CS decreased from 4.84 to 3.77 per million person-years between 2006-2017. The age at diagnosis of CS was 45.3 ± 14.8 years, and 80.0% of the patients were female. Cushing's disease and adrenal CS accounted for 35.4% and 64.6% of patients with CS, respectively. The incidence rate of cancer in patients with CS was 7.77 (95% Confidence Interval [CI] = 5.84-10.14) per 1000 person-years, with an SIR of 2.08 (95% CI = 1.54-2.75). The three most common cancer types were liver (27.7%), kidney (16.7%), and lung (13.0%). Patients with endogenous CS have a higher incidence of cancer.