Hematological malignancy genetic analysis guidelines from WHO, NCCN, and others have centered around structural and copy number variants. This focus has traditionally relied on a combination of three cytogenetic technologies: karyotyping, FISH, and microarray. These traditional methods rely heavily on manual interpretation and require extensive expertise. Optical genome mapping (OGM) consolidates approaches into a single laboratory assay in which the output provides simultaneous analysis of structural and copy number variants. OGM can comprehensively detect these variations genome-wide down to 5% variant allele fraction from fresh or frozen bone marrow aspirates and blood. Laboratory and analytical steps require four to five days from sample to datasets with annotated variant calls, making it an attractive choice for hematologic malignancy genomic analysis. Dynamic filtering in the OGM graphical user interface (Bionano Access™) can be configured to remove polymorphic variants and prioritize the most promising candidates. Subsequently, the software allows analysts to evaluate genome-wide variants and classify each based on relevance. For example: an ALL dataset with t(9;22), deletion of CDKN2A, and whole chromosome gains of 4, 6, and 10 can be loaded into circos plot visualization with pre-defined filters focused on relevant variants. Analysts can then examine and notate each variant independently of one another, then submit completed classifications to a lab director. The director can then adjudicate classifications, leave notes, and download the final output. A variety of cases with hallmark abnormalities from various malignancies will be presented with the filtering and prioritization workflow used to derive them. This comprehensive approach allows for a quicker, more reliable output than traditional cytogenetic approaches.