The yield of echocardiography in cancer patients with acute ischemic stroke is unknown. We identified adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two neurologists independently reviewed all clinical data, including TTE and TEE reports, and adjudicated whether echocardiographic studies revealed a definite or possible source of stroke according to pre-defined criteria. Patients were classified as having suspected cardioembolic strokes if imaging showed embolic-appearing infarcts in more than one vascular territory. Among 220 patients with cancer and ischemic stroke who underwent echocardiography, 216 (98%) had TTE and 37 (17%) had TEE. TTE revealed a definite source in 15 (7%, 95% CI 4-10%) patients and a possible source in 42 (19%, 95% CI 14-25%), while TEE revealed a definite source in 10 (27%, 95% CI 12-42%) patients and a possible source in 14 (38%, 95% CI 21-54%). In 92 patients with suspected cardioembolic strokes who underwent TTE, 6 (7%, 95% CI 1-12%) had a definite source, including 4 with marantic endocarditis, and 20 (22%, 95% CI 13-30%) had a possible source. Twenty-one of these patients also underwent TEE, which demonstrated a definite or possible source in 16 (76%, 95% CI 56-96%) patients, including marantic endocarditis in 4 (19%). The yield of TTE for detecting marantic endocarditis and other cardiac sources of stroke in cancer patients is low, but TEE may provide a higher yield in targeted patients.