Monocytoid B-cell lymphoma, the neoplastic counterpart of the monocytoid B cells, is a now well-recognized variant of low-grade, malignant B-cell lymphomas. However, monocytoid B-cell lymphomas state of differentiation, its cellular origin, and its relationship to other B-cell compartments are still obscure. We investigated an unusual case of monocytoid B-cell lymphoma with generalized disease at presentation, including infiltration of the abdominal lymph nodes, spleen, liver, and bone marrow, as well as involvement of the peripheral blood. The tumor showed the typical sinusoidal and perifollicular growth pattern in the lymph nodes. In the spleen the main infiltrate was confined to the marginal zone. These features and the characteristic immunoreactivity of the tumor cells (KiM1P+, KiB3-) in our case suggest that monocytoid B cells and their neoplastic counterparts are closely related to and probably derived from marginal zone cells.