Acute lymphoblastic leukemia is typically characterized by leukocytosis, resulting from the uncontrolled proliferation of malignant cells. However, we report an atypical case of acute lymphoblastic leukemia that presented with leukopenia and exhibited a protracted clinical course spanning 6 months. The patient, a 45-year-old female, initially presented to our hospital with recurrent fever and was found to have lymphoblasts in a hypoplastic bone marrow. Upon further investigation, the patient was diagnosed with B-cell lymphoblastic leukemia, not otherwise specified, based on cell surface antigen expression and genetic abnormalities. Notably, the patient demonstrated persistently low white blood cell and neutrophil counts, without evidence of increasing lymphoblast infiltration in the bone marrow during the ensuing 6-month period. Subsequent chemotherapy led to normalization of hematopoiesis and disappearance of lymphoblasts, resulting in complete remission of the disease.