Pseudotumor of infancy (POI) occurs within the first month of life as a benign neck mass and affects 0.4% of all newborns. Differentiating these lesions from a malignancy or a congenital anomaly requiring surgical intervention can represent a diagnostic challenge for the clinician. While 80-90% of these masses resolve spontaneously within the first six months of life, there is still considerable time expended and cost incurred in the evaluation of POI. We have established and implemented a protocol for the evaluation of these patients consisting of a complete history and physical exam, ultrasonography and routine follow-up every four to six weeks. Seventeen patients were identified who had been evaluated and followed in the aforementioned manner. Two patients underwent diagnostic imaging studies prior to referral, consisting of magnetic resonance imaging (MRI) and computed tomography (CT). Ultrasonography appeared identical in 80% of the cases of POI with a heterogeneous pattern of internal echogenicity and a hypoechoic surrounding rim. The remaining ultrasound studies differed only subtly with regard to the internal echo pattern. There were no patients with pseudotumor of infancy in whom the ultrasound was normal. We concluded that a work-up including a history and physical exam and ultrasound is an accurate and cost-effective method for evaluating newborns with a neck mass, when suspicious for POI. Ultrasonography has a 100% sensitivity for the diagnosis of POI in this clinical scenario.