Objectives: Radiographic evaluation may assist in diagnosis and surveillance in women with uterine leiomyosarcoma (LMS).Recent studies have shown that the addition of adjuvant therapy after surgical management does not seem to improve survival.Importantly, diagnostic biomarker, which distinguishes malignant tumor LMS and benign tumor leiomyoma (LMA), is not established yet.Experimentally, it is noteworthy that LMP2 deficient mice exhibit spontaneous development of uterine LMS, with a disease prevalence of ~37% by 12 months of age.It must therefore be demonstrated whether human uterine LMS show the weak expression of LMP2.Methods: Immunohistochemistry (IHC) was performed using the avidin-biotin complex method.Sections were incubated at room temperature for 1 h with anti-LMP2 antibody.Afterwards, sections were incubated with a biotinylated secondary antibody and then exposed to a streptavidin complex.Complete reaction was revealed by 3,3,-diaminobenzidine, and the slide was counterstained with hematoxylin.Results: The IHC experiments demonstrated that although normal tissues (24 cases) and LMA tissues (26 cases) markedly expressed LMP2, LMS tissues (32 cases) did not.Conclusions: Defective LMP2 expression is likely to be one of the risk factors for the initiation of human uterine LMS development, as it is in the LMP2 deficient mouse.Thus, LMP2 is useful for a novel diagnostic maker for human uterine LMS.Because there is no effective therapy for unresectable uterine LMS, our results may bring us to specific molecular diagnosis and therapy to treat this disease.