Selective involvement of the B-cell compartment of lymph node by B-cell malignant lymphomas is an occasional finding related to early phases of lymph node infiltration. The authors have observed a unique case of diffuse small lymphocytic lymphoma that consisted of immunohistologically and genotypically proven B-clonal population exhibiting a repetitive pattern of infiltration in three lymph node samples obtained from the patient during a 9-year period. This pattern consisted of a selective and complete replacement of the B-areas with disappearance of follicles and widening of the medullary cords, an expanded T-zone showing features consistent with dermatopathic lymphadenitis and well-preserved sinuses. Clinically, multiple involved sites at presentation (lymph nodes, spleen, skin, bone marrow, and peripheral blood) and during the 9-year follow-up (testis) were detected, and the disease was associated with a relative indolent course like other low-grade lymphomas. The phenotypic profile of lymphoma cells studied by immunoperoxidase method, and by single-labeling and double-labeling flow cytometric analyses (SIg+, K+, LN2+, MB1+, MB2+, HLA-DR+, CD 9+, CD19+, CD 20+, CD 21+, CD 22+, CD 24+, Leu 8+, CD 5-, CD 10-, CD 11b-, CD 11c-, CD 25-, CD 38-, PCA-1-, FMC-7-, CD 23-) was consistent with a B-cell proliferation at an intermediate stage of differentiation but distinct from other well-defined B-cell neoplasms. Whether such unique B-zone pattern was due to an intrinsic property of this lymphoma or it is to be related to the coexisting reactive T-zone expansion remains controversial.