Background/Purpose: Acute lymphoblastic leukemia (ALL) is a heterogeneous hematological neoplasm arising from B and T lymphocyte precursors with diverse genetic alterations. Identifying genetic abnormalities is essential for classification, risk stratification, minimal residual disease monitoring and targeted therapy administration. This extensive study provides details of ALL genetic aberrations in our community and compares these findings with international reference data. Methodology: Analysis for bone marrow aspiration of 568 newly diagnosed ALL patients at King Faisal Specialist Hospital and Research Centre (KFSH&RC) between 2012 and 2016 was carried out through karyotyping and a specific fluorescence in situ hybridization (FISH) panel. Depending on the type and age of newly diagnosed ALL patient, the specific FISH ALL panel was selected out of three ALL panels including; pediatric or adult panels for B-cell ALL or T-cell ALL panel. However, an adolescent age-group (15-19 years) is separated as individual entity. This lead results in a better understanding and concordance with different conflicted epidemiological studies in which a childhood ALL case might be considered with (0-14 years) or (0-19 years). Finally, the collected results were also paralleled to the reference data acquiring from the current World Health Organization (WHO) classification for hematological and lymphoid neoplasms, 2008, and its update 2016. Results: The median diagnosis age was 8 years (range 0.08-89 years) with a male to female ratio 1.5:1 in 568 newly diagnosed ALL patients. There were 118 (21%) cases referred from outside hospital to be diagnosed or in the process of transferring the patient. Cytogenetic and FISH abnormalities were evident in 431 samples (76%) of all cases. B-ALL and T-ALL constituted 489 (86%) and 79 (14%) of all cases. The pediatric ALL cases, excluding the adolescent group, represented 402 (71%) of all cases, of which B-ALL being the clear majority by 360 cases (90%). Cases in age between 15 and 19 years of age were account for only 56 cases (10%) of all cases. The adult-group consisted of 110 patients (19%) of ALL cases with B and T-ALL representing 77% and 23%, respectively (table 1). In the B-ALL group, Philadelphia-positive t(9;21) ALL, KMT2A (MLL) rearrangement, t(12;21) ETV6/RUNX1 translocation, hyperdiploidy, hypodiploidy, t(1;19), intrachromosomal amplification (iamp) 21 and complex groups were detected by classical cytogenetic, FISH or both in 8% (3% in pediatric-ALL, 7% in adolescent-ALL and 31% in adult-ALL), 4% (5%, 2% & 2%), 11% (15%, 0% & 0%), 40% (49%, 19% & 13%), 3% (3%, 7% & 0%), 2% (1%, 9% & 5%), 4% (5%, 5% & 0%) and 4% (3%, 7% & 6%), respectively (table 2). Investigation of genetic abnormalities among newly diagnosed T-ALL revealed only 46 positive cases (58%) with two third of these cases (31 cases) harboring a deletion of chromosome 9 short arm. Conclusion: These enormous data supported the value of applying different diagnostic methods to detect genetic alterations among newly diagnosed ALL patients. In addition, our ALL population show a different pattern of genetic abnormality rates which is evident by a higher rate of hyperdiploidy and lower high risk genetics frequencies. These could have an impact on the relapse and overall survival. Further regional collaborative study between multicenter and correlation with the clinical outcomes are demanded to strengthen these observations and might have a positive effect on our ALL patients. Disclosures No relevant conflicts of interest to declare.