PURPOSE OF REVIEW: Recent discoveries have demonstrated that ovarian cancer is actually composed of multiple separate diseases. Clear cell cancer is an important example. This review will describe the unique biology of clear cell carcinoma, its novel molecular features, and the recent translation of this into new therapeutic approaches. RECENT FINDINGS: Clear cell cancer of the ovary is now recognized as a unique disease. Recent work has shown that a subset of clear cell cancers evolve from endometriosis. The oxidative stress conditions found within endometriotic lesions are likely to contribute to the transformation process. Molecular alterations within clear cell cancers include unique cytokine expression patterns and c-met amplification. Clear cell-specific clinical trials based upon these biologic discoveries have been designed and are presently active. SUMMARY: These studies provide substantive support for a unique clinical management of clear cell cancer of the ovary. Future research will exploit the molecular pathways identified in these tumors in an effort to provide more effective therapies. Presently, agents that target angiogenesis or cellular metabolism would be reasonable therapeutic approaches to these tumors. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.