Abstract Introduction Left atrial (LA) thrombosis usually occurs in patients affected by atrial fibrillation (AF), generally involving the left atrial appendage (LAA). We present the unexpected echocardiographic finding of multiple LA thrombi despite an adequate antithrombotic strategy. Case Presentation A 76–year–old lady underwent transesophageal echocardiographic examination (TOE) to assess eligibility for percutaneous LAA occlusion (LAAO) procedure due to high bleeding risk. Her medical history included AF and a recent percutaneous coronary revascularization; therefore, her antithrombotic therapy included apixaban 2.5 mg bid and clopidogrel 75 mg od. The TOE showed LA structural and functional remodeling with spontaneous echo contrast and multiple thrombi involving the LAA (one [12 x 9 mm] overflowing the orifice and attached to the Coumadin Ridge and the second [12 x 7 mm] attached and arising from the tunnel of patent foramen ovale). Mitral valve stenosis was excluded (Fig.1). Due to TOE findings, the patient was not considered eligible for percutaneous LAAO. Due to the concomitant very high thromboembolic risk, despite the previous intracranial bleeding, we decided to stop apixaban and to start parenteral anticoagulation for 3 weeks with low–molecular weight heparin (100 UI/kg bid) followed by the switch to a vitamin k antagonist (VKA). We also prescribed a hematological evaluation to exclude a hypercoagulability disorder. Our patient’s daughter was a carrier of a mutation in both the methylenetetrahydrofolatereductase and Thrombin genes. A TOE after 30 days showed the persistence of LA thrombi, although with significantly reduced size and mobility (Fig.2). The follow–up was clinically uneventful. We suggested to continue anticoagulation therapy with VKA, and we planned a new TOE after 4 weeks. Discussion Although proper anticoagulation decreases cardioembolic risk in patients with AF, atrial thrombosis may occur due to LA remodeling, high CHA2DS2–VASc score and other factors, including hypercoagulability disorders. The presence of multiple LA thrombi represents a challenge for clinicians, especially in case of concomitant high thromboembolic and bleeding risk. However, the best treatment strategies for these extreme conditions are not defined, so far. Therefore, the therapeutic choice is often tailored to the single patient and based on the clinical judgment, bearing in mind that avoiding Charybdis means passing to close to Scylla and vice versa.