Diagnostic studies of the quantitative composition of the test sample performed in laboratory medicine are based on a number of physico-chemical and bioanalytical methods. Features of the biological material matrix in these measurements can lead to matrix-dependent results for methods of organic analysis and bioanalytical methods, which include measurements of biologically significant parameters of macromolecules or their complexes of biological origin. Application of reference measurement techniques and commutative matrix reference materials in laboratory medicine is the key to obtaining reliable and comparable results, to ensure traceability of measurements. In this article, we have shown the main approaches for development of higher-precision methods in the field of measurements of low molecular weight organic compounds (organic analysis) and measurements of macromolecules and their complexes of biological origin on the example of nucleic acids (bioanalysis). Developed standard samples, traceable to national standards or reference materials of foreign production are presented. The results of VNIIM participation named in international comparisons organized by the working groups of the Consultative Committee on the Quantity of Substances (Analytical Chemistry and Biology) of the International Bureau of Weights and Measures (CCQM BIPM) — the Organic Analysis Working Group and the Nucleic Acid Analysis Working Group. The data characterizing the possibility of measuring a number of diagnostic markers in human serum are presented. The approaches for nucleic acid measurements standardization and ensuring their results traceability to the non-system SI unit, “copy number”, are discussed. Results of participation of VNIIM in international comparisons at the highest level of accuracy provide the basis for ensuring the required traceability for a number of measurements in laboratory medicine at the national level.