BACKGROUND Cutaneous lymphoid infiltrates at sites of herpes zoster scars in patients with B-cell chronic lymphocytic leukemia (B-CLL) often are diagnosed as benign lymphoid hyperplasia ("pseudolymphomas"). The histologic and immunophenotypic features of these lesions are not well characterized. Appearance of skin lesions in B-CLL patients is considered a poor prognostic sign. METHODS Eight punch biopsies from five patients (three males, two females; mean age, 66.7 years) affected by B-CLL and presenting with lesions at sites of previous herpes simplex (upper lip, one patient) or herpes zoster (trunk, four patients; forehead, one patient) infections were included in the study. Histologic examination was performed on routine sections stained with hematoxylin and eosin and Giemsa. Immunohistologic stainings were performed with a standard three-step immunoperoxidase technique on formalin fixed, paraffin embedded tissue sections. RESULTS Specific cutaneous infiltrates of B-CLL were diagnosed histopathologically and immunophenotypically in eight biopsies from all five patients. Clinically, patients presented with erythematous papules or plaques confined to the area of previous herpes virus eruptions. Histopathologic features in most cases were characterized by a variably dense perivascular and periadnexal infiltrate of small hyperchromatic lymphocytes throughout the entire dermis, reaching the subcutaneous fat. In one case, a dense, diffuse infiltrate involving the entire dermis was observed. A granulomatous reaction with presence of epithelioid and multinucleated giant cells was a prominent feature in four biopsies from three patients. Light areas containing large lymphoid cells with features of prolymphocytes and paraimmunoblasts (so-called "proliferation centers") could be observed only in the case characterized by a diffuse infiltrate. Immunohistology revealed an aberrant CD20+/CD43+ phenotype of neoplastic B cells, which is not found in normal B lymphocytes (CD20+/CD43-). Reactive T lymphocytes were present in all lesions and had a normal CD20-/CD43+/CD45Ro+ phenotype. At the time of this writing, four patients were alive without signs of skin disease after a mean follow-up of 58.5 months, and one patient died of B-CLL 24 months after the cutaneous eruption. CONCLUSIONS Specific cutaneous infiltrates of B-CLL are not uncommon at sites of herpes virus scars. The diagnosis can be confirmed by histopathologic and immunophenotypic criteria. The prognosis is better than previously reported.