Malignancies of the hematopoietic system frequently are associated with severe cytopenias requiring transfusions of blood components. Refusal of blood components by Jehovah’s Witnesses (JW) produces challenges to treatment. In this report we describe the outcome of hematological malignancies of JW patients treated without transfusions. Altogether, eight JW, diagnosed 1994-2015, 6 (75%) females, the median age at diagnosis 40 years (range, 20-78), were included into the analysis. The diagnoses were: acute lymphoblastic leukemia (2, 25%), acute myeloid leukemia (2, 25%), non-Hodgkin’s lymphomas (4, 50%). One patient died without treatment while the remaining 7 patients received treatment, including imatinib in 1 patient with BCR-ABL1+ acute lymphoblastic leukemia. Five (62.5%) patients received erythropoiesis stimulating agents. Median hemoglobin concentration at diagnosis was 8.7 g/dL (range, 6.3-13.1), and it decreased to 3.2 g/dL (range, 2.6-9.3) during first-line treatment. Median platelet count at diagnosis was 52 × 109/L (range, 15-392). All patients became thrombocytopenic upon treatment reaching median platelet count 8 × 109/L (range, 2-85). Five patients developed respiratory failure. Anemia contributed substantially to the death of 3 out of 6 patients (50%). One patient (17%) developed central nervous system bleeding in the course of thrombocytopenia. Objective response rate was 43%, with 29% complete remissions after first-line treatment. Despite the median overall survival of 15.3 months (95% CI, 0.2-52.2), all but one acute leukemia patients succumbed shortly after the diagnosis. To conclude, the outcome of JW treated because of hematological malignancies without blood transfusions is very dismal, nevertheless, selected patients can obtain complete remissions. Anemia contributes significantly to the death of JW.