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Enhui Guo,1,2,* Chengqian Li,2,3,* Yanjiao Hu,4 Kongyuan Zhao,1,2 Qingmei Zheng,1,* Liming Wang1,* 1Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Qingdao Medical College, Qingdao University, Qingdao, People’s Republic of China; 3Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingmei Zheng; Liming Wang, Department of Gynecology, The Affiliated Hospital of Qingdao University, No. 1677, Wutaishan Road, Huangdao District, Qingdao, Shandong, 266000, People’s Republic of China, Tel +86-18661806725 ; +86-18661807912, Email zhengqingmei0532@126.com; wlmqingyi@163.comAbstract: Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, is a histological subtype of benign leiomyoma with bizarre cells and nuclear atypia. Differentiating LBN from other benign leiomyoma subtypes, uterine smooth muscle tumors of uncertain malignant potential (STUMP), or leiomyosarcoma (LMS) can be diagnostically challenging owing to overlapping features in clinical presentation and pathologic morphological analysis. The difficulty of distinguishing LBN from other lesions, especially from LMS, and the potential of LBN for subsequent malignant transformation make LBN an important topic of research. Herein, we review the definition, diagnosis, treatment, and prognosis of LBN. Histopathological examination is essential for distinguishing LBN from other diseases. Pathology sampling and morphological examination remain the key to diagnosis. The newly established ancillary immunohistochemical (IHC) and molecular genetic analysis can be useful tools for differential diagnosis. Furthermore, serum biomarkers and imaging examination may also be useful d