Acute neonatal appendicitis is a rare condition associated with significant morbidity and mortality. The severity of this disease is caused by its tendency to occur more frequently in premature infants, an increased perforation rate with rapid progression to peritonitis, and delay in diagnosis and intervention. Although appendicitis in the perinatal period may occur as an isolated event, in many cases it occurs in association with other pathologic states, including prematurity, inguinal hernia, and others. The presentation of neonatal appendicitis can be identical to necrotizing enterocolitis, leading to misdiagnosis. Here we report a case of perforated appendicitis in a 9-day-old boy with tetralogy of Fallot and esophageal atresia with tracheoesophageal fistula. In addition, we present a review of the clinical features of neonatal appendicitis and a discussion of previously described, associated conditions.