We reported a case of non-bacterial thrombotic endocarditis (NBTE) in a 37-year-old woman who presented with signs and symptoms of cardio-embolic cerebral stroke caused by a prothrombotic state due to underlying advanced uterine cancer. Multimodal imaging, including 3D-ecocardiography, as well as laboratory and cultural tests, were critical in making the diagnosis. After starting anticoagulation therapy with low molecular weight heparin (LMWH), the patient underwent surgical aortic valve replacement due to worsening aortic valve function, initial left ventricle enlargement, increasing dimensions, and mobility of vegetations. Unfortunately, vegetations relapsed on the aortic valve bio-prosthesis as well as the mitral leaflets, resulting in a final picture of multi-valve NBTE. The fatal outcome was due to a massive multiple limb embolism, which resulted in leg amputations and septical complications. Starting with the case, we present a brief overview of the pathology's presentation, treatment, management, and prognosis, as well as the diagnostic work-up.