Objective: To investigate the expression of phosphatase of regenerating liver-3 (PRL-3) in ectopic, eutopic, and normal endometria and explore its relationship with endometriosis. Design: A clinical retrospective and molecular study. Setting: Department of obstetrics, gynecology, and reproductive medicine. Patient(s): One hundred and five women with histopathologically confirmed endometriosis, and 50 women with histopathologically assessed normal endometria. Intervention(s): Immunohistochemical staining and Western blot analysis. Main Outcome Measure(s): Expression of PRL-3 protein. Result(s): As shown by the immunohistochemical analysis, PRL-3 was mainly located in the cytoplasm and membrane. The cells that tested positive for PRL-3 were detected in endometriotic tissues that did not occur in eutopic and normal endometria. Statistical analysis indicated that the expression of PRL-3 was closely associated with the clinical stages and recurrence of endometriosis. Conclusion(s): Expression of PRL-3 is related to the clinical stages and recurrence of endometriosis, which provides use with a novel marker and promising target in the treatment of human endometriosis. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.