This chapter discusses blood bank testing and procedures in support of hematology–oncology patients. For transfusion safety at the bedside, pretransfusion specimens must be correctly labeled, and blood transfusions must be appropriately confirmed for the patient. The blood bank performs blood grouping and crossmatching to identify compatible red blood cell (RBC) units for transfusion. ABO is the most important blood group system for compatibility due to strong naturally occurring hemolytic anti-A or anti-B when the B or A antigens are not present, respectively. Patients exposed to RBCs through transfusion or pregnancy can produce potentially hemolytic RBC alloantibodies which are sought in antibody screening. Clinically significant alloantibodies require the need for antigen-negative, serologically crossmatch-compatible RBC units to avoid hemolysis. Routine antibody detection is sometimes complicated by immunoglobulin G (IgG) (warm) or cold (IgM) autoantibodies in autoimmune hemolytic anemia or by the presence of daratumumab (anti-CD38). For each of these situations, there are test procedures to inactivate or remove the reactivity so that alloantibodies can be sought. Patients with sickle cell disease should receive RBC units with extended antigen matching and sometimes need rare RBC units due to multiple antibodies or an antibody to a very high-prevalence antigen. Patients receiving an allogeneic hematopoietic stem cell transplant (allo-HSCT) often undergo a blood type switch as their transplant engrafts, and blood banks have a protocol for which ABO or Rh type of blood components are safest to give during the transition. Severe immunosuppression in allo-HSCT, hematologic malignancies, and certain other conditions pose a risk for transfusion-associated graft-versus-host disease, which is prevented by gamma irradiation of RBCs and platelets to inactivate donor leukocytes.