Atrial fibrillation (AF) in the setting of malignancy poses a unique challenge given the confluent pathologies and risks of current treatments. Oral anticoagulation is recommended to reduce the risk of systemic thromboembolism in high-risk individuals with AF. The ‘Watchman’ device for left atrial appendage closure has shown comparable efficacy compared with anticoagulation with warfarin; however, patients with cancer were not included in trials testing Watchman safety and efficacy. We present the current treatment approaches for the management of AF in patients with malignancy. We review contemporary guidelines and propose a novel clinical decision tree by which physicians can consider left atrial appendage closure in cancer patients, and at last, suggest future investigation that might further clarify the clinical benefit of this approach.