Abstract Background: B-lymphoblastic leukemia/lymphoma (B-LL) is the most common childhood cancer. Occasionally, circulating blasts in the peripheral blood are rare ({less than or equal to}1%) and may be missed, even when flow cytometric immunophenotyping is performed, leading to a false negative report. Methods: The records from all patients with a new diagnosis of B-LL at our institution were reviewed from Jan 2009-Dec 2011. Of 130 cases with peripheral blood flow cytometry, 15 had a blast count of {less than or equal to}1%, with 14 having electronic files for gating monocytes. The percentage of monocytes by flow cytometry and absolute monocyte counts (AMCs) were compared with peripheral blood samples that were negative by flow cytometry, sent due to at least one lineage cytopenia (n=39). Results: The monocytes from the patients with leukemia averaged 0.8%, and were statistically lower than the negative controls, which averaged 7.1% (p<0.001). 11 of the 14 (79%) patients with leukemia had monocytes <1%, compared to only 3 (8%) of the negative controls. The AMCs were also significantly lower (p<0.001), with 93% of the leukemia group having an AMC of <100 cells/µL, compared to only 28% of the negative controls. Conclusions: In patients presenting with cytopenias, assessment of percentage monocytes may be an important diagnostic clue in determining the presence of occult leukemia. If flow cytometry is performed, acquisition of more than the standard 10,000 events is necessary to adequately assess for leukemia. If monocytes are <1% by flow cytometry in the setting of cytopenias, bone marrow examination is recommended, even with negative peripheral blood flow cytometry.