Background and Objectives: Uterine smooth muscle tumors are the most common human neoplasm .They are divided clinically as benign and malignant but there is another group of lesions which is difficult to place in these two categories ,so-called smooth muscle tumors of uncertain malignant potential (STUMP) and differentiation of these tumors on the basis of H&E staining is impossible . The goal of this study was finding of distinguishing objective biomarkers and a survey of proliferation markers comparing these three groups of tumors. Materials & Methods: Twenty one cases in each group of above mentioned tumors were selected randomly (63cases in total ) from Pathobiology laboratories and studied by using immunohistochemistry (IHC) staining for Ki_67 expression and special Argyrophilic Nucleolar Organizing Regions (AgNOR) staining method. Results : Ki_67 was expressed in 63.15% of leiomyosarcomas (LMS), 4.76% of STUMPs and 0% of leiomyoma group. Ki_67 expression between LMS and STUMP ,and also between LMS and leiomyoma were significantly different(P<0.0001).Mean AgNOR dots were2.55±0.03, 2.55, 0.66,4.04, and 8.12 ±0.13 in leiomyoma, STUMP and leiomyosarcoma,respectively. Significant differences between the three groups were observed (P<0.0001). Conclusion: AgNOR and Ki_67(MIB1) proliferation markers expression between LMS and STUMP were significantly different. Due to difficulty in differentiation LMS from STUMP, finding objective biomarkers is useful and practical. For this purpose, the present study recommend, Ki_67 and AgNOR staining which is a reliable, simple and rapid method.