Thrombophilia is a well-described consequence of cancer and its treatment. The pathogenesis of this phenomenon is complex and multifactorial. Nonbacterial thrombotic endocarditis (NBTE) is a serious and potentially underdiagnosed manifestation of this prothrombotic state that can cause substantial morbidity in affected patients, most notably recurrent or multiple ischemic cerebrovascular strokes. Diagnosis of NBTE requires a high degree of clinical suspicion as well as the judicious use of two-dimensional echocardiography to document the presence of valvular thrombi. In the absence of contraindications to therapy, treatment consists of systemic anticoagulation, which may ameliorate symptoms and prevent further thromboembolic episodes, as well as control of the underlying malignancy whenever possible.