We studied 86 specimens from 24 patients with hairy cell leukemia (HCL) to determine the sensitivity of routine flow cytometry (FC) and consensus primer PCR (cpPCR) in this disease. FC was more sensitive, detecting HCL in 48 (56%) of 86 specimens, while clonal B-cell populations were detected by cpPCR in only 23 (27%) of 86 specimens. FC and cpPCR were both more sensitive than morphologic examination. A positive cpPCR result is associated with higher tumor cell numbers than a negative cpPCR result, as determined by FC (P = .0017). We determined cutoff values for number of tumor cells at which cpPCR is consistently positive. At 6.8 tumor cells per microliter, cpPCR would be expected to be positive in at least 90% of the samples. FC was adequate in 86 cases (100%), while cpPCR was adequate in 74 cases (86%). FC is superior to cpPCR for detecting minimal residual HCL. It is more sensitive and more specific and permits quantitation of tumor cell number.