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Introduction: Myelolipomas are rare, benign neoplasms usually arising from the retroperitoneum. They represent an unusual diagnostic challenge due to their vague GI symptoms. We present a case of an 81-year-old patient complaining of severe dyspepsia. An abdominal CT scan and a fine needle biopsy lead to a diagnosis of giant retroperitoneal myelolipoma. A complete surgical resection was performed; no evidence of recurrent tumor was noted after 10 months.Areas Covered: Giant myelolipomas are very rare lesions. Clinical diagnosis of myelolipomas can be problematic due to their indefinite symptoms. CT scan and fine needle biopsy can be useful to reach a diagnosis, although they cannot be used to exclude malignancy in giant lesions. Surgery is the principal treatment if the tumor is symptomatic or > 7 cm. Follow-up is not mandatory due to the lack of any example of recurrence described in literature.Expert Commentary: Despite the size of the neoplasms, since most of the complaints are vague, patients with this diagnosis should be considered among patients with unexplained gastrointestinal symptoms. Since malignancy cannot be excluded based on preoperative and intraoperative biopsy, an aggressive surgical approach is essential. [ABSTRACT FROM AUTHOR]