We report 23-Year-old male patient, known case of sickle-cell disease, with frequent pain attacks and multiple time admission in the hospital, no history of stroke, priapism and acute chest syndrome was noticed. The patient was given multiple transfusions during the last few weeks. His blood film showed microcytic hypochromic picture with notable presence of sickle cells. His hemoglobin electrophoresis showed Low A1-Hb (17%), F-Hb (8.6%) and S-Hb (69%). The patient was offered related allogeneic BMT as a possible treatment. Patient’s HLA typing for class I and II was performed by using One Lambda sequence specific oligonucleotide reverse and sequence specific primers (SSOr/SSP). Also, 6 family members underwent HLA Typing for Class I and II, including his parents which were noted as possible donors. The parents are cousins. The result is based on haplotype illustration; Patient (A*24,24, B*48,50, C*08,06, DRB1*07:01,07:01, DQB1*03:03,02:02), Father (A*01, 24, B* 50,48, C*06,08, DRB1*07:01,07:01, DQB1*02:02,03:03), Mother (A*24,68, B*51,50, C*15,06, DRB1*04:03,07:01, DQB1*03:02,02:02), Brother (A*24,68, B*48,50, C*08,06, DRB1*07:01,07:01, DQB1*03:03,02:02), Sister-1 (A*24, 24, B*48,51, C*08,15, DRB1*07:01,04:03, DQB1*03:03,03:02), Sister-2 (A*24,68, B*48,50, C*08,06, DRB1*07:01,07:01, DQB1*03:03,02:02), Sister-3 (A*01,24, B*50,51, C*06,15, DRB1*07:01,04:03, DQB1*02:02,03:02). As we could interpret the results the patient has an unexpected unique haplotype. Therefore, all tests were repeated with new samples to exclude possible sampling error. However, the same results were confirmed, so we initiated further investigation study in the family. This showed a crossover in the region of paternal A locus, as the patient showed A*24 instead of expected A*68. The illustration of HLA haplotypes and the significant similarity of HLA typing in class I and II in the parents explained the presence of single mismatch in class I between the patient and his sister-2. Possibility of rare crossover must be considered in the interpretation of unexpected HLA results of families worked up for BMT.