Holstein cows that dairyman love live a long time and produce lots of milk. What is unique about these high-producing, long-lived cows? Obviously, these cows have received good management and avoided major health issues. Are the 50K genetics of these elite cows different from other Holsteins? Elite cows were defined phenotypically as having produced over 68,039 kg (150,000 lb) of milk during their lifetime and were classified as very good (VG) or excellent (EX). Elite cows were born in the decade before 2008. For a control, females born in the decade before 2008 with a 50K Holstein genome evaluation were chosen. Control females either had not produced 68,039 kg of milk during their lifetime or were not classified VG or EX. Genomes (50K or 77K) were available on 823 elite cows and 1,589 control females. Defining elite or control as binomial allowed detection of almost 200 markers that were different in allele frequency between elite cows and control females. The most significant chi-squared for differences in allele frequency between elite cows and control females identified a marker on chromosome 5, which had the largest difference in minor allele frequency of 0.17 between elite and control groups. Basing significance on chi-squared –log₁₀P of 8.000 as a threshold, 199 markers were significant and were distributed across all bovine chromosomes. Minor allele frequencies of elite cows were greater for 140 of these markers and minor allele frequencies of control females were greater for 59 markers. As interpretation, minor allele frequencies define uniqueness. The uniqueness of elite cows was supported by more positive changes in minor allele frequencies for the elite cows. A single “it factor” is insufficient to identify uniqueness of elite cows, but many markers are candidates to contribute to the uniqueness. Because allele frequency differences were found across all chromosomes, balance continues to be important in striving to increase the number of elite cows in the breed.