A 45-year-old woman had asthenia, diffuse myalgias, and mild splenomegaly. Her history included smoking and no evidence of viral illness. There was no family history of lymphoid disorders. Laboratory tests showed lymphocytosis (6.1 × 109/L) that had been present for years without anemia and thrombocytopenia. Peripheral blood smears usually show ~ 10% of the lymphocytes as binucleated (see figure). A polyclonal increase of serum IgM (10.1 g/L) has been present. Immunophenotyping demonstrated a polyclonal population of B lymphocytes (IgM+, IgD+, CD19, CD20, CD27, and FMC7 positivity and CD5, CD10, CD23, and CD43 negativity). Karyotype and FISH revealed an isochromosome for the long arm of chromosome 3, +i(3q), and an acquisition of +3 and +18. Tests for viral infection, hormone abnormalities, and connective tissue diseases have been negative. A diagnosis of persistent polyclonal B-cell lymphocytosis (PPBL) was made and her case has remained stable for 12 years. Although lymphocytosis has