Molecules responsible for embryogenesis are often involved in tumorigenesis. Recent exhaustive cDNA microarray analyses in human neoplasms expanded knowledge of such molecules. Hepatocyte nuclear factor-1beta (HNF-1beta) is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF-1alpha. In contrast to HNF-1alpha, HNF-1beta is very weakly expressed in the liver and is commonly expressed in the kidneys. During human embryonic stage, HNF-1beta plays an important role in organogenesis, especially of the urogenital system. In the human fetus, HNF-1beta expression is common in mesonephric duct derivatives and metanephros (permanent kidneys). HNF-1beta germline mutations cause malformations of these structures. Recent microarray analyses have disclosed that HNF-1beta is aberrantly up-regulated in clear cell carcinoma of the ovary, which is a carcinoma of müllerian nature, but which was initially misnamed "mesonephroma". HNF-1beta is also expressed in ovarian endometriosis, which is a probable origin of clear cell carcinoma. On the other hand, HNF-1beta is down-regulated in renal neoplasms, such as chromophobe cell carcinoma. In this review, we first summarize HNF-1beta expression in the developing urogenital system of the human embryo. Then, we describe the HNF-1beta status in human urogenital neoplasms and discuss its role in tumorigenesis.