People with cancer may be at increased risk for stroke, especially of cardioembolic and large vessel origin. Some clinicians are reluctant to use recombinant tissue plasminogen activator (rTPA) in the cancer population due to safety concerns. We conducted a retrospective review of patients who received rTPA for acute stroke at an academic cancer center. We report six patients with cancer treated with rTPA at our institution, four of whom had early neurologic recovery. Only one of our six patients suffered minor bleeding as a complication of rTPA. Acute stroke in patients with cancer may be treated with rTPA, and active cancer should not be considered an absolute contraindication to rTPA use.