A report on an unusual case of pericardial effusion and tamponade that was found incidentally on myocardial perfusion imaging. This was later confirmed by echocardiography and subsequently treated with pericardiocentesis. Two-dimensional echocardiography is still the "gold standard" for diagnosing pericardial effusion. Nuclear cardiac imaging will probably never have a primary role in the diagnosis of pericardial effusion. However, it may be helpful when the diagnosis of pericardial effusion has not been considered and when this condition is suggested by nuclear imaging findings. The echocardiogram underestimated the amount of pericardial effusion compared to myocardial perfusion imaging in this case, and in contrast to previous published reports. Further, prospective studies need to focus on the sensitivity and specificity of sestamibi nuclear scans in the qualitative and quantitative assessment of pericardial effusions.