Cellular and molecular uniqueness has recently gained eminent importance, due to the large amount of data produced by "-omics" technologies. Herein, we have constructed and decoded the "Uniquome", by introduction of the new peptide entities: (a) "Core Unique Peptide" (CrUP), defined as the peptide whose sequence is accommodated, specifically and exclusively, only in one protein in a given proteome, and also bears the minimum length of amino acid sequence; and (b) "Composite Unique Peptide" (CmUP), defined as the peptide composed by the linear unification of CrUPs, when two or more successive in order CrUPs overlap one another. We have analyzed the human reviewed proteins that are numbered 20,422 in all. We found that 7,271,607 peptides from 4 to 100 amino acids in length, were characterized as CrUPs, in 20,258 human proteins, whereas 164 reviewed proteins (0.80%) were not found to contain any CrUP. Further analysis, revealed that these CrUPs could generate 66,447 CmUPs. Analysis of CrUP structure in relation to their length (number of aa they are composed of) showed that the majority (69.03%) of human CrUPs consist of 6 aa, while 20.6 % and 8.62% of CrUPs are characterized by 5 and 7 aa, respectively. For CmUP species, the analysis unveiled that 11-peptides and 12-peptides strikingly represent the higher CmUP numbers (5.71% and 4.57%, respectively), followed by 10-peptides and 13-peptides (1.81% and 2.56%, respectively).The distribution of CrUPs onto human chromosomes proved that chromosomes exhibit CrUP-coverage values from 90% to 96%, while the mitochondrial chromosome presents 100% -respective- coverage, whereas the Y sex-chromosome is characterized by the lowest CrUP coverage of 32%. The detection of CrUPs in human proteome dictates our emerging ability to reliably identify a protein by use of only one peptide. Towards this direction, we found that 564,148 peptides of the 815,026, trypsin digest-derived, peptides of 20,258 proteins, (69.22%) contained at least one CrUP species herein defined as "Tryptic digest Unique Peptides" ("TUPs"). The detected TUPs originated from 20,136 proteins (99.39%), whereas 122 proteins were found to lack TUP species. To strengthen the biological significance of CrUPs, we unveiled that 89% of Cancer Antigenic Peptides ("CAPs") and 87% of Immune Epitope Peptides ("IEPs") contain at least one CrUP species, while it is demonstrated that 97% of bioactive peptides being included in the PeptideDB database contain at least one CrUP. Taken together, our findings strongly support the potentially beneficial applications of human CrUPs in tissue pathology, therapeutic oncology, and translational medicine. Furthermore, these novel peptide entities seem to play a crucial role for protein identification, protein-function prediction, cell physiology and tissue pathology.