In postmenopausal women, obesity is associated with an increased risk of oestrogen receptor-positive breast cancer. Aromatase converts androgens into oestrogens and its expression within adipose stromal cells (ASCs) is believed to be the major driver of oestrogen-dependent cancers in older women. A number of factors have been shown to increase aromatase expression in ASCs and include the inflammatory mediator prostaglandin E2 (PGE2). Ghrelin is a gut-hormone that is involved in the regulation of appetite. It is produced as a prohormone that is acylated and cleaved to yield ghrelin, known to bind to and activate the cognate ghrelin receptor, GHSR1a. The unacylated form of ghrelin, des-acyl ghrelin, binds weakly to GHSR1a but has been shown to play an important role in regulating a number of physiological processes including glucose homeostasis. We recently sought to determine whether ghrelin and des-acyl ghrelin may have an effect on aromatase in primary human ASCs. Results demonstrate that pM concentrations of ghrelin and des-acyl ghrelin inhibit aromatase transcript expression and activity in ASCs under basal conditions and in PGE2-stimulated cells. Moreover, the effects of ghrelin and des-acyl ghrelin are mediated via effects on aromatase promoter PII-specific transcripts, known to be increased in obesity and breast cancer. The GHSR1a-specific agonist capromorelin and the ghrelin gene by-product obestatin have no effect on aromatase transcript expression or activity. To further support these findings, GHSR1a protein is undetectable by Western blot and neither ghrelin nor capromorelin elicit a calcium response in ASCs. Finally, we found that ghrelin causes a significant decrease in basal and forskolin-stimulated cAMP in ASC. Considering that cAMP is central to the regulation of aromatse PII in obesity and breast cancer via effects on CREB and CREB-related pathways, these findings provide a mechanism for the inhibition of aromatase by ghrelin. Our findings also suggest that ghrelin acts at alternate ghrelin receptors in ASCs and that ghrelin mimetics may be useful in the treatment of oestrogen-dependent breast cancer.