Abstract Background Cardiac masses (CM) represent a heterogeneous clinical scenario. Sex-related differences of these patients remain to be established. Purpose: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. Material and Methods Thestudy cohort included 321 consecutive patients with cardiac mass enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause death at follow-up was evaluated. Multivariable regression analysis was performed to assess potential prognostic disparities between men and women. Results Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p=0.02) than men. Regarding CM histotypes, females were more frequently affected by benign masses (with cardiac myxoma above all), while metastases were more common in men (p<0.001). At presentation, peripheral embolism occurred predominantly in women (p=0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, at multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignancy and peripheral embolism resulted independent predictors of mortality. Conclusion In a large cohort of heart masses, a significant sex-related difference in histotype prevalence was found: benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex does not influence prognosis in benign and malignant masses.