Pericardial effusion may occur as a result of malignant pericarditis, which may in turn result in cardiac tamponade. This paper reports on a rare case of cardiac tamponade that occurred in an African American patient with breast cancer and neurofibromatosis. Herein, we present a case of a 38-year-old woman with neurofibromatosis type 1 (NF1) and breast cancer. She presented with sudden shortness of breath and hypotension. Computed tomography of the chest and an echocardiogram confirmed the presence of cardiac tamponade. Symptomatic relief was obtained following an emergency pericardiocentesis. The patient experienced a recurrence of symptomatic pleuro-pericardial effusion, requiring repeat therapeutic pericardiocentesis and thoracocentesis. To eliminate accumulating fluid, an indwelling drain was placed. The clinical condition of the patient, however, continued to deteriorate and she expired a few days after admission. When patients with breast cancer present with dyspnea, clinicians should maintain a high index of suspicion of cardiac tamponade; urgent imaging should be performed to exclude tamponade. Further research is needed to identify the factors that predict cardiac tamponade in breast cancer patients as well as the optimal treatment for the condition. It is also necessary to examine the relationship between a history of neurofibromatosis and cardiac tamponade.