Terminal tissue differentiation and function of slan monocytes in cancer is largely unexplored. Our recent studies demonstrated that slan monocytes differentiate into a distinct subset of dendritic cells (DC) in human tonsils and that slan cells colonize metastatic carcinoma-draining lymph nodes. Herein, we report by retrospective analysis of multi-institutional cohorts that slan cells infiltrate various types of non-Hodgkin lymphomas (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, including the most aggressive, nodal and extranodal, forms. Nodal slan cells displayed features of either immature DC or macrophages, in the latter case ingesting tumor cells and apoptotic bodies. We also found in patients with DLBCL that peripheral blood slan monocytes, but not CD14 monocytes, increased in number and displayed highly efficient rituximab-mediated antibody-dependent cellular cytotoxicity, almost equivalent to that exerted by NK cells. Notably, slan monocytes cultured in conditioned medium from nodal DLBCL (DCM) acquired a macrophage-like phenotype, retained CD16 expression, and became very efficient in rituximab-mediated antibody-dependent cellular phagocytosis (ADCP). Macrophages derived from DCM-treated CD14 monocytes performed very efficient rituximab-mediated ADCP, however, using different FcγRs from those used by slan macrophages. Our observations shed new light on the complexity of the immune microenvironment of DLBCL and demonstrate plasticity of slan monocytes homing to cancer tissues. Altogether, data identify slan monocytes and macrophages as prominent effectors of antibody-mediated tumor cell targeting in patients with DLBCL. slan monocytes differentiate into macrophages that function as prominent effectors of antibody-mediated tumor cell targeting in lymphoma. http://cancerres.aacrjournals.org/content/canres/78/13/3544/F1.large.jpg .