Supermagnetic Iron Oxide Nanoparticles (SPIONs) are nanoparticles that have an iron oxide core and a functionalized shell. SPIONs have recently raised much interest in the scientific community, given their exciting potential diagnostic and theragnostic applications. The possibility to modify their surface and the characteristics of their core make SPIONs a specific contrast agent for magnetic resonance imaging but also an intriguing family of tracer for nuclear medicine. An example is 68Ga-radiolabeled bombesin-conjugated to superparamagnetic nanoparticles coated with trimethyl chitosan that is selective for the gastrin-releasing peptide receptors. These receptors are expressed by several human cancer cells such as breast and prostate neoplasia. Since the coating does not interfere with the properties of the molecules bounded to the shell, it has been proposed to link SPIONs with antibodies. SPIONs can be used also to monitor the biodistribution of mesenchymal stromal cells and take place in various applications. The aim of this review of literature is to analyze the diagnostic aspect of SPIONs in magnetic resonance imaging and in nuclear medicine, with a particular focus on sentinel lymph node applications. Moreover, it is taken into account the possible toxicity and the effects on human physiology to determine the SPIONs' safety.