The authors present two cases of diffuse brainstem lesions that regressed without treatment. Two newborns presented with cranial nerve palsies and limb weakness at birth. Magnetic resonance (MR) images obtained in the 1st week of life revealed a large, expansive pontomedullary lesion in each patient. Findings of clinical and imaging examinations were highly consistent with the characteristics of diffuse brainstem glioma. After consultation with the parents of both infants, all parties agreed to forgo the treatment modalities available at the time. Neither patient underwent surgery, radiation treatment, or chemotherapy; both underwent routine neurological and MR imaging examinations. Within weeks the patient in Case 1 started to improve clinically and at 4 years of age has reached nearly all developmental milestones. Serial MR images demonstrated a steady decrease in the size of the lesion. The patient in Case 2 improved in a similar manner and is now 10 years old. The findings from these two cases should encourage families and clinicians to consider that a subcategory of diffuse lesions may exist, particularly in the neonatal period. It must be stressed, however, that nearly all patients with diffuse brainstem lesions experience a poor outcome, regardless of tumor grade or treatment. Brainstem gliomas, spontaneous regression of central nervous system tumors, and the differential diagnoses of brainstem lesions are discussed.