As part of an effort to develop a better understanding of the relationship between nodal monocytoid B-cell lymphomas (MBCLs) and follicular lymphomas (FLs) when they coexist (MBCL + FL) and to assess the validity of the morphological criteria for the latter diagnosis, we evaluated follicular colonization, bcl-2 reactivity, light chain restriction, and the presence of t(14;18) in 14 benign lymph node specimens containing benign monoclonal B cells (MBCs), in eight nodal specimens of pure MBCL, and in 17 nodal specimens of MBCL coexisting with FL (MBCL + FL). Follicular colonization by malignant MBCs was observed in six specimens of pure MBCL and in 13 specimens of MBCL + FL. Benign MBCs did not express bcl-2 by immunohistological methods in 11 of 12 benign specimens. In contrast, weak reactivity for bcl-2 was detected in malignant MBCs in four of five specimens of pure MBCL and in the MBCL component in 13 of 15 specimens from the MBCL + FL group. In the FL component of 13 specimens, the bcl-2 was strongly positive. Identical light chain restriction was detected by immunohistological methods in both the FL component and the MBCL component in 15 specimens of MBCL + FL. Polymerase chain reaction analysis did not detect the t(14;18) translocation in any of 10 benign specimens or any of six evaluable pure MBCL specimens. In contrast, the translocation was detected in whole sections from eight of 12 specimens of MBCL + FL. Thus, on the one hand, the high incidences of follicular colonization and the coexistence of MBCL and FL as well as the identical light chain restriction in MBCL and FL components of MBCL + FL cases suggest that possibly these are related closely when they coexist. On the other hand, the bcl-2 and t(14;18) data cannot be used as evidence in support of a close relationship.