Smooth muscle tumors are histologically separated into benign leiomyomas and malignant leiomyosarcomas. Uterine leiomyomas represent benign clonal tumors often arising within the smooth muscle tissue of the human uterus. Uterine leiomyomas develop after the start of the menstrual cycle, become symptomatic during middle age, and in most postmenopausal patients tumor regression occurs. Rarely, leiomyomas progress to leiomyosarcomas, where many sarcomas have markedly reduced or no steroid hormone receptors, thus, evolve to a hormone non-responsive state. Premenopausal leiomyomas are known to express higher levels of estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta) and progesterone receptor (PGR) than control myometrium, whereas postmenopausal leiomyomas have not been so well characterized molecularly. In this present investigation, ERbeta, ERalpha and PGR gene expression were assessed in leiomyomas and in matched adjacent myometrium from a cohort of 14 postmenopausal patients using semi-quantitative Realtime PCR and RT-PCR. The mean average results showed that ERbeta was 2.5-fold statistically significantly over expressed in postmenopausal leiomyomas compared to patient matched myometrium (p=0.038), whereas ERalpha and PGR were not significantly differently expressed. These results showed that up-regulation of ERbeta occurred at the transcriptional level in postmenopausal leiomyomas. Quantitation of steroid hormone receptors from benign uterine tumors may be important for a more tailored therapy. In addition, a role for steroid hormones, specifically ERbeta, is discussed in terms of benign tumor regression or tumor maintenance in postmenopausal leiomyomas.