Congenital defect of the muscular layer of the small intestine is a rare cause of spontaneous bowel perforation in premature infants. During the last 12 years we have observed four similar cases. We describe the most recent one, a premature infant who developed two abdominal events. On her 2nd day of life, spontaneous perforation of the distal ileum due to focal absence of the muscular layer occurred. Several weeks later she developed the typical clinical and histological picture of necrotizing enterocolitis. The clinical and histological characteristics of the two different conditions are compared, and the 24 cases reported in the literature are discussed. We conclude that focal absence of intestinal musculature may be not such a rare entity as is commonly believed.