Patients with a left atrial (LA) thrombus are considered at risk of a serious thromboembolic event, and therefore endocardial radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is contraindicated. However, RFCA of AF is inevitable in some patients with highly symptomatic AF and suspicious LA masses resembling thrombus. A patient was treated who underwent hybrid epi- and endocardial RFCA for drug resistant, highly symptomatic, paroxysmal AF with a suspicious left atrial (LA) thrombus that was a lamellated, thickened, echogenic lesion attached to the LA anterior wall and resistant to anticoagulation. During RFCA, contact with the LA endocardium was minimized using hybrid epi- and endocardial ablation guided by computed tomography merged with 3-dimensional electroanatomical mapping (NavX). The patient has been free of AF without antiarrhythmic drugs for 6 months, therefore hybrid epi- and endocardial ablation may be an effective therapy for AF patients with a LA mass.