OBJECTIVES: Despite being the most common pelvic tumor in women, little is known about the molecular basis of uterine leiomyoma growth. The purpose of this study was to (1) identify genes important for leiomyogenesis by comparing gene expression in leiomyoma and normal myometrium and (2) examine the expression level of selected genes on a larger panel of leiomyomas. METHODS: The technique of mRNA differential display (DD) was used to perform a larger survey of gene expression in leiomyoma by comparing it to matched normal myometrium. Transcripts differentially expressed in leiomyoma were sequenced and further analyzed. Selected differentially expressed transcripts were used as probes on RNA blots of 20 pairs of leiomyomas and their matched myometria to evaluate their expression. The level of expression was analyzed by densitometry. RESULTS: From 80 differentially expressed transcripts picked by DD, 30 were sequenced and compared to GenBank data. Selected transcripts were analyzed for mRNA levels on a panel of 20 pairs of leiomyomas and matched normal myometria. One transcript that matches the early response gene EGR1 was found to be dramatically reduced (9.2 times on average) in leiomyomas. The reduction was present in 100% of the tumors. CONCLUSIONS: mRNA differential display is a valid method for finding differences in gene expression between leiomyoma and normal myometrium. The consistency and level of EGR1 mRNA reduction in leiomyoma is an indication that this gene may play a role in the origin or growth of leiomyoma.