We reported here a case of persistent polyclonal B-cell lymphocytosis (PPBL) in a 31-year-old female patient. Peripheral blood smears showed atypical binucleated lymphocytes which were polyclonal B-cells with kappa and lambda expression, and without clonal rearrangement of immunoglobulin heavy chain. Cytogenetic analysis found a trisomy 8, with premature chromosome condensation. Clinically, PPBL is associated with moderated splenomegaly, adenopathy, and smoking. It remains to be established whether PPBL is a real pathology or a simple cytological abnormality.