Four unusual cases of sudden and unexpected cardiovascular death in infancy and early childhood that were found during a ten-year autopsy review at our institutions are presented. In Case 1, an asymptomatic 2-year-old male, sudden death resulted from an acute myocardial infarct due to occlusion of coronary arteries that had been previously damaged by unsuspected arteritis. Case 2, a previously well 7-month-old male, died from an acute myocardial infarct due to an unsuspected anomalous origin of the coronary arteries from a single, stenotic coronary ostium. Case 3, a previously well 21-month-old black male, died from a splenic sequestration crisis due to undiagnosed sickle cell disease. Case 4, a 2-month-old female with suspected Marfan syndrome, died from a ruptured dissecting aneurysm of a patent ductus arteriosus. Accuracy of diagnosis was of particular importance in the latter two cases because of the possible genetic implications.