Background: The link between the effects of recombinant human growth hormone (rhGH) therapy in patient with growth hormone deficiency (GHD) and Chiari malformation type I (CM-1) is controversial. Summary: We report the case of a patient with an unusual association of growth hormone deficiency (GHD) due to ectopic posterior pituitary and Chiari malformation type I (CM-1). Our patient developed headache and worsening of CM-1 after initiation of rhGH therapy. Following an atlo-occipital decompression surgery, the patient was able to resume therapy with a marked growth improvement. Based on this observation, we provide a systematic review of the current literature about these two pathologies. Key Messages: A careful follow-up of all patients with CM-1 treated with GH is mandatory, paying particular attention to the appearance of any neurological signs and symptoms.