Introduction: Ectopic secretion of GHRH is a rare cause of acromegaly. However, its recognition is clinically important because different therapeutic approaches are required. Case Presentation: We present a challenging case of acromegaly secondary to ectopic GHRH secretion from pancreatic neuroendocrine tumor in a 52-year-old female. The patient is treated with different modalities which include pegvisomant in an attempt to control the stimulated GH-axis considering the limited data about its use in treatment of ectopic acromegaly. Conclusion: GHRH-secreting tumor is a rare cause of acromegaly. Surgical resection of the tumor is the therapy of choice whenever possible. However, further studies are warranted for unresectable tumor or resistant cases.