The aim of this study was to describe the occurrence of acute coronary syndromes in 3 cases of rituximab infusions. We reviewed the records of 3 patients with lymphoproliferative disorders who experienced acute coronary syndromes associated with their initial infusion of rituximab. All 3 patients received rituximab according to a standardized institutional rate schedule, and all received pre-medication with acetaminophen and diphenhydramine. The median age of patients was 61 years. One patient had known atherosclerotic heart disease, and 2 patients had risk factors for coronary artery disease. All patients had varying degrees of evidenced high tumor burden, including lymphocytosis, elevated lactate dehydrogenase values, bulky tumor masses, and bone marrow involvement by lymphoma. All 3 patients experienced fairly typical chest pain syndromes and experienced elevations of cardiac enzymes consistent with myocardial ischemia. One patient died of an arrhythmia that deteriorated into asystole, and 2 patients recovered and underwent coronary angiography. Acute coronary syndromes can be associated with the infusion of rituximab. Patients with a history of previous coronary artery disease or risk factors for coronary artery disease should be observed closely for signs of myocardial ischemia, particularly during the initial infusion. The occurrence of symptoms that could be ascribed to an acute coronary syndrome should always be taken seriously during the first rituximab infusion and investigated aggressively. Patients should be aware that this is a rare, albeit serious, complication of treatment with rituximab.