Spontaneous neonatal pneumomediastinum (PNM) is associated with the aspiration of blood or meconium and birth-related trauma and it seems to be more frequent in post-term newborns. It is generally asymptomatic, but it is occasionally accompanied by mild tachypnoea. Only rarely, it requires oxygen therapy or develops into pneumothorax. To evaluate the relationship between the radiological and clinical diagnosis in this uncommon problem, from January 2005 to August 2009, 35 newborns with spontaneous PNM were enrolled in the study. Treatment protocol provides for execution of a chest X-ray, clinical check, SatO(2) and heart rate monitoring. Clinical diagnosis was accomplished particularly early, within the first 24 h of life. Paraphonic and distant tones discovered by cardio-auscultatory exam disappeared within the following 72 h. A total of 28 newborns were asymptomatic (80%); seven were symptomatic (20%); five had transient tachypnoea of the newborn; two developed an RDS, with Silverman score ≥ 3 and required O(2) therapy. It is necessary to affirm the importance of early diagnosis of this condition, carrying out careful monitoring of newborns at risk, to begin timely therapeutic treatments, as oxygen-therapy and to heighten alertness for complications, such as pneumothorax.