IntroductionNonbacterial thrombotic endocarditis (NBTE) is a rare cardiac manifestation in patients with advanced malignancies of the lungs, pancreas, gynecological system, and gastrointestinal tract. It is often confirmed postmortem by histopathological evidence of sterile platelet‐fibrin deposits attached to the endocardium, most often on heart valves. To the best of our knowledge, our case is the first to report multiple heart lesions caused by the systemic effect of cholangiocarcinoma.Case PresentationWe report the case of a 53‐year‐old male who presented with a stroke; extensive imaging studies, including transthoracic echocardiography (TTE), 2D/3D transesophageal echocardiography (TEE), cardiac multi‐slice computed tomography, and cardiac magnetic resonance, found masses on the mitral valve, the aortic valve, and in the right ventricle, with the largest diameter 43 × 11 mm, which led to a diagnosis of NBTE secondary to presumed cholangiocarcinoma. Combining different echocardiography techniques, including TTE and TEE in specific clinical contexts, and training echocardiographers to improve TEE interpretation skills could be the most cost‐effective option for early diagnosis, particularly in limited‐resource settings, where advanced imaging modalities are not widely applicable.ConclusionsNBTE can manifest in patients with advanced cancer. A high index of clinical suspicion is of central importance for the diagnosis of NBTE, especially through an identification of the underlying predisposing conditions. A multi‐disciplinary approach is crucial for NBTE optimal diagnosis and treatment. As in our patient, multimodality imaging plays a complementary role in clearly defining the nature of cardiac lesions.