Background It remains unclear whether the characteristics of ischemic stroke in patients with cancer (ISC) differ from usual ischemic strokes (non-ISC). Although a small number of studies have been conducted to characterize ISC, the status of cancer has rarely been considered seriously. Aims We aimed to investigate the features of ISC according to the status of cancer, and compare their characteristics with those of non-ISC. Methods We assessed and classified 204 ISC patients into two groups: 104 with active (ISC-active) and 100 with inactive (ISC-inactive) cancer. For each ISC patient, two age- and gender-matched ischemic stroke patients without history of cancer were selected as non-ISC control subjects. We compared the clinical/laboratory data, stroke mechanisms, and diffusion weighted imaging (DWI) lesion patterns between ISC-active and non-ISC patients, and between ISC-inactive and non-ISC patients. Results ISC-active patients demonstrated higher C-reactive protein (CRP) and D-dimer, more frequent cryptogenic stroke and patterns of multiple DWI lesions (in bilateral anterior or in anterior and posterior circulations), and less prevalent conventional risk factors than non-ISC patients, while ISC-inactive patients revealed no such marked differences. Among ISC-active patients, both elevated CRP and D-dimer levels were associated with cryptogenic mechanism and multiple lesion patterns. Furthermore, ISC-active patients with cryptogenic strokes tended to have multiple lesion patterns and metastasis. Conclusions ISC-active, but not ISC-inactive, is distinct in terms of risk factors, stroke mechanisms, and lesion patterns. Chronic inflammation and an activated coagulation system may contribute to the pathogenic mechanism of strokes, the extent of each depending on the activity and severity of cancer.