Cancer develops when cells accumulate genetic changes that allow them to grow uncontrollably, and especially in the case of leukemias, which are among the most common types in the Western world, it has long been known that cytogenetic changes— meaning changes at the chromosomal level — are often critical for diagnostic and prognostic purposes. Understanding the genetic fingerprint of a leukemia case helps to determine the exact type of disease, predict its course, and guide treatment decisions. Identification of these genetic changes is therefore very important in clinical practice. Traditionally, different lab techniques have been used to detect these changes, each with its own strengths and limitations. Karyotyping gives a broad overview of all chromosomes but can miss smaller abnormalities. FISH uses fluorescent probes to highlight specific known changes but can’t detect unexpected ones. Chromosomal micro-array analysis (CMA) or CNV sequencing scans the complete genome for chromosomal imbalances, but does not allow detection of balanced chromosome alterations. A new method called Optical Genome Mapping, or OGM, combines the strengths of these older techniques by isolation and stretching out ultra-long strands of DNA from cancer cells, marking them at fixed points, and comparing them to a healthy reference genome to detect differences. This approach does not require living cells and is able to scan the whole genome in detail in one single experiment. In this thesis I explored whether OGM delivers on its theoretical promise by asking three key questions: first, whether OGM reliably detects all important abnormalities found by traditional methods and what might still be missed. Second, whether OGM offers real added value in diagnosing and classifying different types of leukemia; and third, whether the technique could lead to overdiagnosis by picking up changes that aren’t actually existing/relevant. The findings show that OGM is technically strong and usually matches or even outperforms older methods, although it does have some blind spots, like difficulty in detecting certain chromosome patterns such as polyploidy. Therefore, some results may still need to be double-checked with classic methods. When it comes to added value, OGM proves useful across many types of leukemia, often uncovering additional relevant changes that can even shift the classification of a patient’s disease from one group to another based on genetics rather than microscopic appearance alone. It also helps to assess the overall genetic complexity of a tumor more precisely. As for the risk of overdiagnosis, some studies suggest caution, but with the right interpretation frameworks in place, this concern seems manageable. As can be read in the discussion section, the biggest challenge for bringing OGM into everyday clinical use is the lack of standardized guidelines for how labs should filter, analyze, and report results. However,recently published international guidelines have been an important first step toward in creating this common framework. Once these standards are widely adopted, there should be few remaining barriers for the use of OGM routinely in the analysis of blood cancers, as long as its limitations are kept in mind and traditional techniques remain available for support whenever needed. As mentioned, uncovering the cytogenetic profile of a leukemia is becoming increasingly important—not only for diagnosis but also for determining a patient’s eligibility for targeted therapies. The far more comprehensive genetic landscape enabled by use of OGM is likely to reshape our understanding of cytogenetics. The discovery of novel aberrations may fundamentally alter existing leukemia classifications. It is entirely possible that no classification system currently based on karyotyping or FISH will remain intact. The relevance of these potential changes stems not just from to the relatively high incidence of leukemia in Western populations, but also because of the often profound impact a leukemia diagnosis has on a patient’s life. Take, for example, acute lymphoblastic leukemia (ALL): while prognosis is significantly better in children (with a 5-year survival rate of approximately 90%, compared to 20–40% in adults), an ALL diagnosis still carries a substantial psychological burden and involves intensive therapy—even for very young children. Moreover, ALL accounts for 25% of all cancer cases in individuals under the age of 15 *. This morbidity burden in children should not be underestimated, alongside the high mortality rates seen in both acute myeloid leukemia (AML) and ALL in adults. So on the patient-level, refining cytogenetic classification systems by OGM could give access to more precise prognostic information, enabling more efficient and effective treatment decisions. Given this added therapeutic relevance, OGM may ultimately help reduce leukemia-related mortality across various subtypes—beyond its diagnostic and prognostic value.