Aim Ever increasing novel HLA allele discoveries raise in questions about the clinical relevance of these new alleles and their implications of further working on the donor searching process without compromising the timing of patient’s treatment. Our purpose is to bring attention to the novel allele discovery and provide helpful information to clinicians to make timely and right decisions on hematopoietic stem cell transplantation. Method HLA class I and class II high resolution (HR) typing for recipients and donors were performed by Sequence Based Typing (SBT) methodology. When a novel allele was detected, we examined its clinical significance in three locations: (1) peptide binding grooves; (2) T cell Receptor contacting area; (3) HLA Epitope-specific positions. Results Seven novel alleles and two confirmatory alleles (highlighted) have been identified in our routine HLA HR typing by SBT (see table). The position and the substitution of each novel allele was identified and listed on the table. Pocket Residue, TCR accessibility to HLA antigen and Epitope specificity were also described in the table. Conclusions/Discussions Taken together, our analysis suggest thats: (1) a mutation of a silent point mutation without change in amino acid would be considered as clinically irrelevant (C∗08:02:08); (2) a mutation located outside of α1 and α2 domains of HLA class I or outside of β1 of HLA class II and not HLA Epitope-specific should be considered as clinical insignificant (C∗07:308). (3) a mutation located inside of α1 or α2 domains of HLA class I or inside of β1 of HLA class II could be considered having less clinical relevance if it does not falls into one of the following three criteria: (a) accommodating any peptide-binding pockets, (b) being TCR accessible or (c) being HLA Epitope specific (∗44:173, C∗03:183, C∗04:158 and C∗16:39:02); however, it would be considered having potential clinical relevance if it falls into one of those three criteria (DQB1∗03:45, DQB1∗03:48 and DQB1∗06:49).