Background and Methods-To assess the precise mechanisms of stroke in cancer patients, we analyzed the data for cancer patients with acute ischemic stroke registered from 6 centers in South Korea. Clinical features, risk factors, diffusion-weighted imaging lesion patterns, and laboratory findings including D-dimer levels were compared between patients with conventional stroke mechanisms (CSMs) and cryptogenic group. Results-A total of 161 patients were included in this study: 97 (60.2%) patients in the CSM group and 64 (39.8%) in the cryptogenic group. Patients in the CSM group were older and vascular risk factors were more prevalent than in the cryptogenic group. Diffusion-weighted imaging patterns of multiple lesions involving multiple arterial territories were observed more frequently in the cryptogenic group than in the CSM group. In addition, levels of the D-dimer were higher in the cryptogenic group than in the CSM group (11.5Ϯ14.6 versus 3.6Ϯ10.3 g/dL). In multivariate analysis, the diffusion-weighted imaging lesion pattern of multiple vascular territories (odds ratio, 11.2; 95% CI, 3.74 to 33.3), and D-dimer levels of Ͼ1.11 g/dL (odds ratio, 10.6; 95% CI, 3.29 to 33.8) were associated independently with the cryptogenic group. Conclusions-Stroke outside of CSM occurred in a large number in cancer patients. In stroke patients with cancer, D-dimer levels and diffusion-weighted imaging lesion patterns may be helpful in early identification of non-CSMs (especially coagulopathy associated with cancer) and possibly in guiding preventive strategies for stroke. (Stroke. 2010;41:798-801.)