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Uterine leiomyomas are a common finding in medical practice, but their frequency changes drastically when contextualized in a syndrome, as in the following case. A 50-year-old woman with a known Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome presented at our clinic with abdominal pain located in the lower quadrants and scarcely responsive to analgesic therapy. A twisted gynecological pelvic mass was diagnosed, and management for prompt resolution was adopted. Histologically the mass was described as a leiomyoma. The aim of the present study is to share our experience and to review the literature to compare different manifestation of the disease and different approach used in the various centers. The additional novelty of the paper is the immunohistochemical study we carried out on the leiomyoma that is contrasted with the current etiopathogenetic theories.