The continuous release of anthropogenic pollutants into marine environment increase the needs for the development of analytical procedures for their accurate determination in many sample types. Sound strategies for seafood safety monitoring call for measurement systems capable of producing comparable analytical results with demonstrated quality. Method validation, traceability and uncertainty of analytical results are the three milestones to assess data quality. Some trace elements are essential for biological structures, but they can become toxic at concentrations beyond those necessary for their functions; others, are toxic even at very low levels. Their accurate determination in reference samples serves as an important step in seafood safety control and pollution monitoring.Isotope Dilution Inductively Coupled Plasma Mass Spectrometry (ID ICP-MS) has been applied for the determination of the total mass fractions of five trace elements (Cd, Cu, Hg, methyl mercury (MeHg), Pb, and Zn) in marine biota candidate reference material IAEA-476. Because of the complex matrix of the sample and the expected spectral interferences, special care was taken for the validation of the applied methodology, particularly for its measurement step. Reference isotopic measurements were carried out by Sector Field Inductively Coupled Plasma Mass Spectrometer (ICP-SFMS).The entire ID ICP-SFMS measurement procedure was described by mathematical modelling and the combined uncertainty of measurement results estimated. All factors influencing the final results and isotopic equilibrium were systematically investigated. This included the procedural blank, the moisture content in biota samples and all factors affecting the blend ratio measurements (i.e., instrumental background, spectral interferences, dead time, mass discrimination effects as well as the repeatability of measured isotope ratios).Modeling of the entire measurement procedure and the use of appropriate certified reference materials (CRM) enable to assure the traceability of obtained values to the International System of Units (SI).Finally, the developed procedure has been successfully applied in the process of the certification of the International Atomic Energy Agency (IAEA) certified reference material for trace elements and MeHg mass fractions in fish homogenate sample. The excellent agreement between obtained results in the present study and those derived from the IAEA certification campaign for trace elements and MeHg in the same sample matrix further validated the reference methods developed in the IAEA.