We report a case of malignant mesenchymal spindle-cell neoplasia of the skull, diagnosed in a female newborn at 13 days of age by biopsy and subtotal resection. Considering the good clinical condition, the age, tumor histology and the risks associated with surgery and chemotherapy, we proposed a “wait and see” approach with a close radiologic monitoring of the tumor lesion. Surprisingly the tumor showed spontaneous regression both at MRI and ultrasound evaluations. To date, after 12 months of observation, MRI showed sustained remission: the infant recovered from surgery and maintains good clinical condition while follow-up is ongoing.