In vivo assessment of the outcome of cancer therapy is hampered by the paucity of imaging probes that target tumors specifically and noninvasively. The importance of such probes increases with the continuous development of chemotherapeutics and the necessity to evaluate their effectiveness in a clinical setting. We have recently reported on a dual-modality imaging probe specifically targeting the underglycosylated mucin-1 tumor-specific antigen (uMUC-1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. This probe consists of crosslinked superparamagnetic iron oxide nanoparticles (CLIO) for MR imaging, modified with Cy5.5 dye (for near infrared optical fluorescence imaging (NIRF)), and has peptides (EPPT), specifically recognizing uMUC-1, attached to the nanoparticle's dextran coat. In the present study, we demonstrated that this probe could not only detect orthotopically implanted preclinical models of adenocarcinomas but could also track tumor response to chemotherapy in vivo in real time. Considering the high cost associated with the development and testing of new cancer therapeutics and the need for accurate, noninvasive assessment of their effectiveness, we believe that the developed probe represents a valuable research tool relevant to clinical discovery. © 2005 Wiley-Liss, Inc.