Pancreatic hamartomas are extremely rare tumors in adults and even more so in children. They are lesions characterized by acinar, islet and ductal components found in varying proportions and in a disorganized pattern. We report a case of a premature female with trisomy 18 diagnosed by amniocentesis. The newborn was delivered by cesarean section at thirty-three weeks of gestation and expired within one hour of birth. Postmortem examination exhibited numerous features associated with Trisomy 18 including lanugo on the torso and arms, micrognathia, microstomia, left low-set ear with small flat pinna, closed ear canal, clenched fists with overlapping fingers, rocker-bottom feet, narrow pelvis, large right diaphragmatic hernia and left pulmonary hypoplasia. Microscopic examination of the pancreas revealed an area, 1.2 cm in greatest dimension, with branching ducts and cysts lined by cuboidal epithelium intermingled within primitive mesenchymal proliferation and exocrine glands. The cysts measured up to 0.2 cm and were surrounded by a collarette of proliferating spindle cells as highlighted by Masson’s trichrome stain. A diagnosis of pancreatic hamartoma was rendered. A total of thirty-four cases of pancreatic hamartomas have been reported in the literature including twenty-seven in adults, five in children and two in newborns. Our case may be the third pancreatic hamartoma reported in association with Trisomy 18. We recommend that careful examination of the pancreas be performed in individuals with Trisomy 18 to further characterize this lesion as one of the possible abnormal findings associated with this syndrome.