Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a multifunctional protein kinase expressed abundantly in the central nervous system. Because changes in intracellular Ca2+ concentrations affect progression through the mitotic cell cycle, enhanced expression of CaMKIV has been reported in small cell lung carcinoma and hepatocellular carcinoma. To elucidate the involvement of CaMKIV in endometrial carcinogenesis, we analyzed serial frozen sections from 31 patients with endometrial carcinoma and 20 patients with normal endometria for CaMKIV protein expression, using fluorescent immunohistochemistry. We analyzed the relationship between the percentages of CaMKIV stained cells and the patient characteristics, including clinical stage, histological grade, myometrial invasion, and clinical outcome. In the normal endometria, CaMKIV was detected in none of the cases examined. Most of the CaMKIV proteins were found in the nucleus of endometrial carcinoma tissue. CaMKIV expression was significantly associated with clinical stage (stage I and II versus stage III and IV; p<0.01), myometrial invasion (no myometrial invasion versus the presence of invasion to greater than one-half the myometrium; p=0.02), and clinical outcome (no evidence of disease versus died of disease; p=0.04). Scoring on the basis of the percentage of positive cells indicated that CaMKIV expression was significantly associated with PCNA-labeling index (p=0.02). Our results demonstrate that CaMKIV expression in endometrial carcinoma correlates with the malignant potential of this tumor.