Stroke prediction scores have not been validated in patients with cancer and atrial fibrillation (AF). We aimed to identify unique risk factors and evaluate validity of CHADS2 and CHA2DS2-VASc scores to predict risk of stroke and mortality. A retrospective review of all patients with cancer with pre-existing AF presenting from 2008 to 2014 was performed. Outcomes included ischemic stroke and mortality. Prognostic factors were identified with Fine and Gray regression for stroke and Cox proportional hazards analysis for survival. After excluding patients with hemorrhagic strokes, 2,037 patients were analyzed. Genitourinary cancers were the most common (29%) followed by gastrointestinal cancers (18%). Overall, 52% had CHADS2 ≥2. At a median of 6.4 months, 74 patients (3.6%) developed an ischemic stroke. Increased CHADS2 score was associated with stroke (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.19 to 1.67; p <0.001).