Despite advances in non-invasive medical imaging, accurate nodal staging of malignancy continues to rely on surgery. Superparamagnetic iron oxide nanoparticles (IONP) with lymphotropic qualities have shown some promise as contrast agents for MRI of the lymph nodes, but recent large-scale studies failed to show consistent detection of tumours below 5 mm. Herein we compare imaging of splenic and lymph node tissue using iron/iron oxide core/shell nanoparticles (Fe NP) that have superior magnetic qualities to IONP, to determine whether improved negative contrast in T(2)-weighted MRI can enhance the diagnosis of small tumours in the reticuloendothelial system. To provide an in vivo pre-clinical model of human lymph node micrometastases, breast cancer cells were injected into the spleens of mice, providing localised areas of tumour growth. MR images of groups of tumour-bearing and sham-treated animals were generated using a 1.5 T imaging system and analysed by two independent, blinded radiologists. Fe NP improved the sensitivity and specificity of MRI when compared to IONP, enabling accurate detection of tumours as small as 1-3 mm. The use of Fe NP as contrast agents have the potential to improve the diagnostic accuracy of MRI in cancer patients, leading to more rapid and effective treatment.