Background: Lysosomal protein transmembrane 4 β-35 (LAPTM4B-35), a novel oncoprotein that belongs to the mammalian 4-tetratransmembrane spanning protein superfamily, has been implicated in oncogenesis and cancer progression in several solid malignances. However, the expression of LAPTM4B-35 and its role in endometrial cancer progression remain unknown. Materials and Methods: We investigated the expression of the LAPTM4B-35 protein by immunohistochemistry in 30 normal endometrium specimens and 165 endometrial carcinomas and analyzed its correlation with various clinicopathologic features, including patient outcome. Results: LAPTM4B-35 immunoreactivity was overexpressed in endometrial carcinoma cases compared with normal endometrium (P < 0.001). High LAPTM4B-35 expression was found in 117 (70.91%) of these 165 carcinomas and was positively correlated with the International Federation of Gynecology and Obstetrics stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence, but not with age and histological type. Patients with high LAPTM4B-35 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of LAPTM4B-35 (P = 0.001 and P = 0.002, respectively). Multivariate analysis showed that high LAPTM4B-35 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with endometrial carcinoma (both P = 0.005). Conclusions: These results showed that high LAPTM4B-35 expression was associated with progression and prognosis of endometrial carcinoma. Copyright © 2010 by IGCS and ESGO.