Estrogen sulfatase is a microsomal enzyme and is ubiquitously distributed in several mammalian tissues, among which the liver, placenta, and endocrine tissues exhibit relatively high activity. Because the major circulating precursors of estrogen are estrone 3-sulfate and dehydroepiandrosterone 3-sulfate, estrogen sulfatase plays an important role not only in their incorporation and metabolism, but also in the controls of estrogen activity by regulating the binding potential of estrogen as to its receptor through sulfoconjugation and desulfation reactions. Accordingly, an increase in sulfoconjugation through transfection of the sulfotransferase gene or inhibition of estrogen sulfatase by specific inhibitors has been successfully applied to abolish the estrogen activity in estrogen-dependent breast cancer- and uterine endometrial adenocarcinoma-derived cells. Inhibitors of estrogen sulfatase are expected to be developed as new drugs for estrogen-dependent cancer therapy, particularly in postmenopausal women.