Uterine leiomyomas are the most common tumors in the human female pelvis and the leading indication for pelvic surgery. Lack of understanding of the molecular pathogenesis of leiomyoma has put severe limitations on the availability of alternative treatments. Using an oligonucleotide micro-array-based hybridisation analysis we observed a group of genes with a broad range of functional activity differentially expressed in smooth muscle cells (SMC) derived from leiomyomas when compared to matched myometrial cells. Among them, two IFNα inducible genes, TRAIL and IFI27, were underexpressed in leiomyoma vs. myometrial cells. Expression levels of TRAIL and IFI27 were also measured in myometrial and leiomyoma cells by real-time quantitative PCR in basal condition and after IFNα stimulation. In both cell types, the transcription of the two genes resulted induced by IFNα but the IFI27 transcription stimulation was weaker in leiomyoma than myometrial cells whereas the TRAIL transcription stimulation resulted stronger in leiomyoma respect myometrial cells. Based on this finding and on previous observations we have hypothesized that a reduced response to IFNα stimulation might be involved in leiomyoma formation and growth.