Background/Aim: To investigate the expression and value for diagnosis of the genes, p53 and pTEN, the protein, Ki-67, and the receptors, estrogen and progesterone, in differentiating smooth muscle tumors of the uterus. Material and Method: Seventeen samples of leiomyosarcoma, 2 smooth muscle tumors with uncertain malignant potential (STUMP), 9 atypical myomas and 15 leiomyomas were stained immunohistochemically. The χ2 test was used for the statistical analysis of the data. Results: The malignant side of the spectrum was strongly stained for Ki-67 and p53 while uniformly decreasing toward the benign tumors. The results were found to be statistically significant (p < 0.0001). The staining for progesterone receptor was also statistically significant, but the tumors that were considered benign, such as leiomyoma and atypical myoma, were the ones strongly stained (p = 0.005). The expression of estrogen receptor was significant in these tumors, but the p value was very close to the cut-off value (p = 0.07). As the degree of differentiation of the tumor increased, the trend showed stronger staining for estrogen receptor. However, no difference was detected in the staining properties of the tumors for pTEN (p = 0.2457). Conclusion: The expression of Ki-67, p53 and progesterone receptors is promising in immunodifferentiation of smooth muscle tumors of the uterus with malignant potential. Copyright © 2005 S. Karger AG, Basel.