Objectives: To clarify the role of specific genetic alterations in the multi-step process of malignant transformation of endometriosis. Methods: In cases of ovarian endometrioid carcinoma, we separated regions of normal endometriosis, atypical endometriosis and ovarian endometrioid carcinoma by laser microdissection, and examined K-ras mutation and microsatellite instability in each separated tissue sample. Results: We detected K-ras mutation and microsatellite instability in endometrioid carcinoma tissue, but not in normal or atypical endometriosis bordering the cancerous region. Conclusions: The present findings suggest that K-ras mutation and microsatellite instability are associated with malignant transformation from atypical endometriosis to ovarian endometrioid carcinoma. (C) 2004 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.