As prostate cancer is the second leading cause of cancer death in men in the USA, the clinical challenge is to develop methods that allow early diagnosis, accurate staging and precise treatment. Metastases to local and distant lymph nodes play a major role in the choice of therapy and in predicting outcome of these patients ( 1 Wilkinson BA Hamdy FC State-of-the-art staging in prostate cancer. BJU International. 2001; 87: 423-430 Crossref PubMed Google Scholar ). Clinical examination to detect lymph node metastases alone is inadequate and surgical dissection and serial histologic examinations are currently accepted “yardsticks”. In the past years, there has been debate about the pros and cons of total lymph node resection, particularly because of its morbidity, lengthiness of the surgical procedure and the resources necessary for complete pathologic evaluation of harvested nodes ( 2 Paul DB Loening SA Narayana AS Culp DA Morbidity from pelvic lymphadenectomy in staging carcinoma of the prostate. J Urol. 1983; 129: 1141-1144 Abstract Full Text PDF PubMed Scopus (71) Google Scholar ). Non-invasive imaging techniques for the detection of lymph node metastases would be of great help and a potential cost savings (imaging study vs. surgical lymphadenectomy) in the evaluation and re-staging of cancer patients. All current cross sectional imaging techniques (US, CT and MRI) have a relatively low sensitivity in detecting nodal metastases primarily because detection relies on insensitive size criteria (>10 mm short axis) ( 3 Rorvik J Halvorsen O Espeland A Haukaas S Inability of refined CT to assess local extent of prostatic cancer. Acta Radiol. 1993; : 39-42 Crossref PubMed Google Scholar ). Ultrasmall superparamagnetic iron oxide (USPIO) is a relatively new RES targeted MR contrast agent that is known for lymph node uptake ( 4 Anzai Y McLachlan S Morris M Saxton R Lufkin R Dextran-coated superparamagnetic iron oxide, an MR contrast agent for assessing lymph nodes in the head and neck. AJNR Am J Neuroradiol. 1994; 15: 87-94 PubMed Google Scholar , 5 Anzai Y Prince M Iron oxide-enhanced MR lymphography: the evaluation of cervical lymph node metastases in head and neck cancer. J Magn Reson Imaging. 1997; 7: 75-81 Crossref PubMed Scopus (86) Google Scholar , 6 Harisinghani M Saini S Slater G Schnall M Rifkin M MR imaging of pelvic lymph nodes in primary pelvic cancer with USPIO (Combidex). 1997 Contrast Medical Research Conference. Acad Radiol, Kyoto, Japan1997 Google Scholar , 7 Harisinghani MG Saini S Weissleder R et al. MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: radiographic-pathologic correlation. AJR Am J Roentgenol. 1999; 172: 1347-1351 Crossref PubMed Scopus (154) Google Scholar , 8 Harisinghani MG Saini S Hahn PF Weissleder R Mueller PR MR imaging of lymph nodes in patients with primary abdominal and pelvic malignancies using ultrasmall superparamagnetic iron oxide (Combidex). Acad Radiol. 1998; 5 (discussion S183–164): S167-169 Abstract Full Text PDF PubMed Google Scholar , 9 Bellin MF Roy C Kinkel K et al. Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles—initial clinical experience. Radiology. 1998; 207: 799-808 PubMed Google Scholar , 10 Bellin R, Kinkel K, Challier E, et al. MR lymphography with ultrasmall iron oxide particles in patients with urologic and pelvic cancer. European Congress of Radiology. Vienna, 1997 Google Scholar , 11 Weissleder R Elizondo G Wittenberg J Lee A Josephson L Brady T Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assesing lymph nodes with MR imaging. Radiology. 1990; 175: 494-498 PubMed Google Scholar , 12 Weissleder R Heautot J Schaefer B et al. MR lymphography: Study of a high-efficiency lymphotrophic agent. Radiology. 1994; 191: 225-230 PubMed Google Scholar , 13 Weissleder R Elizondo G Wittenberg J Rabito C Bengele H Josephson L Ultrasmall superparamagnetic iron oxide: Characterization of a new class of contrast agents for MR imaging. Radiology. 1990; 175: 489-493 PubMed Google Scholar ). The purpose of this study was to evaluate the utility of USPIO (Combidex™ Sinerem®) induced signal intensity changes in lymph nodes for staging patients with prostate cancer. Also assessed was the utility of postcontrast images alone in characterizing lymph nodes.