We have previously shown that corticotrophin-releasing hormone (CRH) inhibits the proliferation of Ishikawa (IK) human endometrial carcinoma cell line through the activation of CRH-R1 receptors. Here, we have further investigated the role of CRH and its type-1 receptor in the control of IK cell function, and we carried out a pilot study in tumor tissues obtained from 19 patients with endometrial cancer, looking at CRH-R1 gene expression. In the IK study, CRH counteracted the increase in cell proliferation caused by estradiol; type-1 receptors mediating this effect belong to the alpha subtype. In the study on human tumors, CRH-R1 was expressed in 4 out of 19 (21%) surgical specimens obtained from untreated patients with a diagnosis of primary endometrial cancer. Two out of 4 cases (50%) expressing CRH-R1 mRNA had extrauterine spreading of the disease, whereas cases not expressing CRH-R1 mRNA were all FIGO stage I, 2 (p=0.015).