Follicular dendritic reticulum cells (DRCs) are known to be normally present in primary follicles and both follicular centres and mantle zones of secondary follicles of peripheral lymphoid tissue. Involved frozen biopsy tissue specimens from eight cases of intermediate lymphocytic lymphoma/mantle zone lymphoma (ILL/MZL); eight cases of follicular centre cell lymphomas (FCCL) of the centroblastic/ centrocytic type; and seven cases of well-differentiated lymphocytic lymphoma (WDLL) consistent with chronic lymphocytic leukaemia (CLL) were analysed immunohistologically with R4/23 (DRC-1) monoclonal antibody reactive with ‘bystander’ DRCs. As opposed to FCCL and most WDLL/CLL cases, the DRCs consistently formed a loose, ill-defined meshwork with a radiating or blurred outline in all MZL cases and one ILL. On the basis of the observed findings as well as from those reported in literature, the hypothesis is proposed that ILL/MZL originates from the follicular mantle zone and represents a distinct lymphoma entity owing to its peculiar immunostaining pattern of DRCs that allows it to be separated from both FCCL and WDLL/CLL. Moreover, the absence of DRCs in the microenvironment of other B-cell malignancies such as prolymphocytic leukaemia and hairy cell leukaemia, analogously with most CLL cases, would speak in favour of their different—possibly extrafollicular— compartment of origin within lymphoid tissue.