In cancer, cell division and metastasis require the coordinated activity of a wide range of metal-containing biomolecules, such as proteins, implicated in structural support, enzymatic reactions and electron transfer. Over the last years, modern analytical techniques allowed a better understanding of the cancer biochemistry by acquiring information on the genome, transcriptome, proteome and metabolome. In this project, the metallome –i.e. the ensemble of all metal-containing biomolecules– is in the focus of attention. Novel methodology based on the use of ICP-mass spectrometry (ICP-MS) will be developed for identifying and quantifying the metal(loid)s present at the levels of tissues, individual cells and vesicles (secreted cellular fragments involved in intercellular communication). Spatially resolved information at a tissue level will be obtained via laser ablation–ICP-MS bio-imaging at high spatial resolution. Individual cells will be characterized by single-event ICP-MS. Size-based fractionation of vesicles with asymmetric-flow field-flow fractionation will enable their metal(loid) assembly to be studied. The use of an ICP-MS instrument with a time-of-flight mass analyzer will provide information on the entire elemental mass range in a quasi-simultaneous manner, even when dealing with short transient signals. This focus on metal(loid)s has the potential to provide an enhanced biochemical insight and to discover metal(loid) signatures with prognostic/predictive utility.