Comprehensive genomic profiling (CGP) for patients with advanced solid tumors is on the trajectory of becoming standard of care through incorporation into clinical practice, professional society guidelines, availability of an FDA-approved assay, and a national coverage determination from Medicare. For hematologic malignancies, the clinical utility of CGP can be diagnostic, prognostic, or predictive depending on the type of malignancy. Molecular testing has been standard of care for many years for hematologic malignancies, and payer coverage of the CGP approach must now be considered to keep pace with advances in the field of hematology-oncology. Based on American Medical Association CPT coding definitions, molecular testing for hematologic malignancies is categorized as testing for individual genes and gene panels of 5–50 genes or >50 genes. Our review of payer coverage policies from the Policy Reporter database in October 2018 demonstrated that payer coverage for >50 genes in hematologic malignancies is limited. As an example of coverage limitations, a recently updated Medicare Local Coverage Determination limits coverage to 50 genes or less. Coverage decisions such as these are being made during a time of increasing demand for an expanded approach. Data from the Foundation Medicine, Inc. database shows that as of April 2018, over 3,600 patients with AML, MDS, and MPN have undergone clinical testing with FoundationOne Heme, a CGP assay for hematologic malignancies. In an analysis of over 1,300 AML cases tested with FoundationOne Heme, 62% had an alteration that is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and 91% had a clinically relevant alteration identified that could inform diagnosis, prognosis, or treatment selection. In an analysis of over 1,300 MDS cases tested, 70% had at least one clinically relevant alteration identified. In an analysis of over 200 MPN cases tested, 48% were triple negative for CALR, JAK2, and MPL, and of those triple negative cases, 55% had another clinically relevant alteration. These data demonstrate that FoundationOne Heme is a clinically important assay for patients with hematologic malignancies including AML, MDS, and MPN, and stakeholders within the system must now come together to further refine the clinical utility, improve payer coverage, and ensure patient access to this impactful testing as the field advances.