Nanotechnology is poised to have a substantial influence on biomedicine. A unique example of a nanotechnology that has progressed from proof-of-concept to human clinical trials is the use of ultrasmall superparamagnetic iron oxide nanoparticles as a cell-specific contrast agent for MRI. When injected systemically, these particles are taken up by macrophages of the reticuloendothelial system and accumulate in lymph nodes. This passive, cell-specific targeting of the iron oxide nanoparticles to lymph nodes, and the differential cellular content of benign versus malignantly infiltrated nodes make this method suitable for cancer staging. By using lymphotropic nanoparticle enhanced MRI, differences in benign versus malignant infiltration of lymph nodes can be visualized, which adds accuracy to standard MRI beyond criteria based solely upon the size and shape of lymph nodes. This technology has been used to assess lymph node metastases in a large number of human cancer types. In this Review, we focus on lymphotropic nanoparticle enhanced MRI and its application for the staging of genitourinary malignancies.