Background: Validations of routinely used serological typing methods require intense performance evaluations typically including large numbers of samples before routine application. However, such evaluations could be improved considering information about the frequency of standard blood groups and their variants. Meth-ods: Using RHD and ABO population genetic data, a Caucasian-specific donor panel was compiled for a performance comparison of the three RhD and ABO serological typing methods MDmulticard (Medion Diagnostics), ID-System (DiaMed) and ScanGel (Bio-Rad). The final test panel included standard and variant RHD and ABO genotypes, e.g. RhD categories, partial and weak RhDs, RhD DELs, and ABO samples, mainly to interpret weak serological reactivity for blood group A specificity. All samples were from individuals recorded in our local DNA blood group typing database. Results: For ‘standard’ blood groups, results of performance were clearly interpretable for all three serological methods compared. However, when focusing on specific variant phenotypes, pronounced differences in reaction strengths and specificities were observed between them. Conclusions: A genetically and ethnically predefined donor test panel consisting of 93 individual samples only, delivered highly significant results for serological performance comparisons. Such small panels offer impressive representative powers, higher as such based on statistical chances and large numbers only.