We studied skewing of light chain ratios (LCRs) in germinal center cells (GCCs) relative to mantle cells (MCs) by flow cytometry (FC) in 98 reactive lymphoid tissues. LCRs were assessed using a 4-color lambda/kappa/CD20/CD38 tube. GCCs and MCs were discriminated by CD20 and CD38 density. Of 98 cases, 65 contained distinct GCCs and MCs. Light chain expression usually was dimmer on GCCs than on MCs; in 22 cases, the kappa and lambda clusters converged and accurate LCRs could not be determined. Of the remaining 43 cases, the mean GCC LCR was 1.78 (range, 1.10-3.07) vs 1.56 (range, 1.00-2.24) in the MCs (P = .001). The overall kappa/lambda ratio in cases containing GCCs and MCs was 1.65 (range, 1.18-2.69) compared with 1.46 (range, 1.00-1.98) in cases containing MCs only. Of 43 cases, 19 (44%) showed differences of 20% or more between the LCRs of GCCs and MCs. LCRs of GCCs and MCs may differ substantially in reactive lymphoid tissues. These subsets may form distinct clusters and skews in their LCRs and should not be misinterpreted as evidence of occult lymphoma.