Symptomatic intracerebral hemorrhage (sICH) is the most concerning complication of intravenous thrombolysis with recombinant tissue plasminogen (rTPA) occurring in 6% of cases and is associated with a 50% mortality. The presence of pre-thrombolysis cerebral microbleeds (CMB) is considered a risk factor for sICH and poor functional outcome but there is still lack of evidence on the significant impact of CMB number and anatomical distribution. To date, there are no reports describing the relationship between brainstem microbleeds and post-thrombolysis sICH. We report a case of a 47 year old male diagnosed with acute ischemic infarcts on the left corona radiata and left posterior internal and external capsule, with five CMBs – one on the right temporal lobe, another on the right thalamus, and three in the pons. He was given Intravenous (IV) rTPA within 20 min post-ictus with initial improvement of deficits. However, on the second hour post-rTPA, there was clinical deterioration with evidence of intraparenchymal hemorrhage on the left frontal lobe and pons. This case report highlights the presence of chronic brainstem microbleeds as a potential predictor of sICH and a valuable factor when deciding on giving IV rTPA in acute ischemic stroke.