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Background: Although ischaemic stroke with malignancy occasionally occurs, the mechanisms of stroke in such cases have not been investigated in detail. Objective: To examine the mechanisms of ischaemic stroke with malignancy, particularly in relation to right-to-left shunt (RLS). Methods: Consecutive patients with ischaemic stroke within 24 h of stroke onset were prospectively studied. Contrast saline transcranial Doppler examination was carried out for all patients, to investigate the presence of RLS. When patients with stroke had RLS, deep venous thrombosis (DVT) or pulmonary embolism was assessed to diagnose paradoxical brain embolism. Results: Participants comprised 184 consecutive patients (115 men and 69 women) with a mean (standard deviation (SD)) age of 73 (11.8) years and mean (SD) National Institutes of Health Stroke Scale (NIHSS) score of 8 (7.4). RLS was detected in 32 of 184 (18%) patients. Malignancy was present in 11 (5%) patients. RLS was more frequent in patients with malignancy than in patients without malignancy (55% v 15%, respectively; p = 0.001). All six patients with RLS and malignancy displayed DVT or pulmonary embolism with severe disability (modified Rankin Scale 4–5) before stroke onset. Conclusion: Paradoxical brain embolism should be considered to be an important mechanism in patients with stroke and malignancy.