It seems possible that small lymphoma cells (SLC) may have a role even in aggressive B-cell non-Hodgkin's lymphoma (B-NHL) such as large-cell lymphoma. However, SLC are often difficult to distinguish morphologically from normal or reactive small lymphocytes. In this study, we used a flowcytometric technique (kappa-lambda imaging; KLI) for detection of SLC. Peripheral blood (PB) and bone marrow (BM) samples taken from 41 patients with surface immunoglobulin positive (sIg+) B-NHL were analysed. SLC were detected in about 90% (37/41) of the untreated patients when either PB or BM was analysed by KLI. The presence of SLC correlated well with disease activity. However, a few SLC were present even in the PB (16%) or BM (27%) of the 31 patients who achieved complete remission, indicating that minimal residual disease (MRD) was present. In some cases, the reappearance of SLC in the PB or BM preceded clinical relapse. Furthermore, the initial volume of SLC, particularly in the BM, tended to be related to the prognosis (P = .068). These results suggest that the detection of SLC by KLI may be helpful not only for the screening and clinical staging of sIg+ B-NHL, but also for monitoring disease activity and detecting MRD. Moreover, the volume of SLC in the BM may be a useful predictor of prognosis.