The proliferating component in chronic lymphocytic leukaemia (CLL) is usually small (<1%) and restricted to a specific micro-environmental niche. To characterize the proliferating component, CLL cells from bone marrow or lymph nodes of 23 patients were assessed for expression of up to 66 surface antigens in combination with nuclear Ki-67/MCM6. Ki-67 expression was associated with step-wise increases in CD23/CD95/CD86/CD39/CD27 and decreases in CD24/CD69/CXCR4/CXCR5. Ki-67+ cells showed increased CD38 expression, but with considerable inter-patient variability: in some cases Ki-67 expression was only detectable in CD38− CLL cells. The results suggest continuous re-entry into the cell cycle as no distinct stem cell pool was detectable.