The relative expression levels of estrogen receptor α (ERα) and mitochondrial cytochrome b (MTCYB) transcripts and their association with ERα, -397T > C gene polymorphism was determined in premenopausal uterine leiomyomas and myometrium tissues to gain an insight into the role of ER-mediated action of estrogen on mitochondrial gene transcription. Both ERα and MTCYB transcripts were overexpressed in leiomyomas compared with myometrium tissues with 9.18 ± 0.79 folds and 5.24 ± 0.48 folds, respectively. ERα demonstrated ≥1.7 folds overexpression expressed over MTCYB (p < 0.001). Genotype correlation with transcript expression revealed that leiomyomas with CC genotype had significantly increased levels of ERα with 11.9 ± 1.02 folds as compared with 6.46 ± 0.56 folds seen in CT and TT genotypes together (p < 0.001). Interestingly, MTCYB transcript levels were also >1.9 folds overexpressed in leiomyomas with the CC genotype as compared with leiomyomas with other genotypes (p < 0.01).Significant elevation of ERα and MTCYB transcript levels in premenopausal leiomyomas and its association with ERα, -397 CC genotype suggests the mitochondrial-mediated role of estrogen as the promoter of leiomyoma tumorigenesis.