The presence of a cerebral cavernous malformation (CM) is generally not regarded as an exclusion criterion to the use of intravenous tissue plasminogen activator (tPA). However, there is a conceivable risk of hemorrhaging with an intracerebral CM, which may dissuade clinicians from treating stroke patients with systemic tPA in the presence of a CM. The case of a 79-year-old man with acute ischemic stroke treated with systemic tPA in the setting of known CM is presented. The patient tolerated intravenous thrombolysis well and remained clinically stable throughout the observation period. This is the first reported case (to our knowledge) supporting the notion that systemic thrombolysis is safe in presence of a previously clinically silent CM.