The use of measurement uncertainty among clinical laboratories becomes widespread. Measurement uncertainty can be reported with the result, as well as be used in certain reference change value (RCV) calculation equations. RCV is especially recommended for use in tests with a low individuality index. In our study, we calculated the measurement uncertainty of AFP, CA 125, CA 15-3, CA 19-9, CEA tumor markers with the ISO TS 20914:2019. We compared results with limits. Two Beckman Coulter DXI-800 (Minnesota, USA) autoanalysers' results were used. We calculated the RCV values using the classical Fraser method, logarithmic Lund Method, and Clinical Laboratory Standards Institute (CLSI) method as Minimal Difference (MD). We found the same permissible measurement uncertainty limit as 15.97% for all five tumor markers. The highest RCV value was found as 90% upstream for AFP test with Lund logarithmic approach, the lowest RCV value was found as 12% for CEA with MD, all other RCV results were between these two values. We do not recommend the use of MD, as values for Biological variation are not used in the MD approach. We also recommend using the logarithmic approach, although it gives higher results. There are also clinical studies on the significance of tumor markers in a follow-up that show different results. These differences may be because the studies are conducted with different systems. Therefore, each laboratory needs to calculate its own RCV values. We also recommend informing the clinicians about the tests with high measurement uncertainty.