This novel bead-based compensation approach estimates and corrects for interference between mass cytometry channels. The method simplifies development of new antibody panels, increases flexibility for antibody-metal pairing, opens the way to using less pure isotopes, and improves overall data quality. Based on the same idea in flow cytometry, controls stained with single antibodies are used to estimate signal crosstalk. In application, control samples stained with individual antibodies can be generated by staining polystyrene antibody-capture beads.