Nanoparticles have been designed as novel contrast media for the evaluation of diseases. Ultrasmall iron oxide particles (USPIO) is a novel nanoparticle contrast medium, which is currently being evaluated as an MR lymphographic agent for the assessment of tumor spread to lymph nodes. Nodal disease is an independent poor prognostic indicator in patients with rectal cancer. Accurate pre-operative MR identification of patients with nodal disease and other adverse features can prompt the use of chemoradiation to downsize and downstage the disease, with the aim of reducing the long term risk of local and distant recurrence. In this article, we discuss the challenges to accurate nodal staging of patients with rectal cancer, and demonstrate how USPIO may be applied to rectal cancer imaging to identify nodal involvement.