Staging and monitoring of pediatric acute lymphoblastic leukemia (ALL) includes examination of the cerebrospinal fluid (CSF). At our institution, we noted an increased incidence of low-level leukemic blasts in CSF samples from patients with ALL. This increase coincided with a conversion from the Shandon CytoSpin 4 (Thermo Fisher Scientific, Waltham, MA) to the Wescor Cytopro Rotor AC-060 (Wescor, Logan, UT). This study directly compared these 2 machines using patient samples and known concentrations of cultured leukemia cells. With patient samples, the Wescor Cytopro led to a 5- to 9-fold increase in the number of cells on a slide compared with the Shandon CytoSpin; furthermore, leukemic blasts were detected only with the Wescor Cytopro in 2 cases. Similar findings were observed using cultured leukemia cells. Thus, the detection of blasts in CSF is highly instrument-dependent. The newer, more sensitive cytocentrifuge machines identify blasts that were previously missed by older machines, but the clinical significance remains under investigation.