One hundred and twenty‐nine patients with chronic lymphocytic leukemia (CLL) followed in our outpatient department for periods ranging from 6 months to 13 years were divided into five anatomico‐clinical stages: stage O (peripheral and bone marrow lymphocytosis); stage I (stage O + lymph node enlargement); stage II (stage O + palpable spleen); stage III (stage I + II); and stage IV (anemia or thrombocytopenia). Analysis of actuarial survival curves revealed the following: 1) median survival of the entire population exceeded 114 months; 2) there was no difference between the curves of stage O and stage I patients, 3) there was a significant difference between survival for stage III and IV patients as compared with stages O, I and II (p < 0.01); and 4) median survival for stage III and stage IV was 70 months; and 23 months, respectively. Age did not appear to be a prognostic factor. Prognosis was poorer in male patients and in those with a high initial lymphocyte count (50,000/mm³), but this was due to the higher incidence of stages III and IV in this population (p < 0.01). It was not possible, from this study, to draw any conclusions as to the beneficial effect of chlorambucil in the treatment of this disease. However, in patients treated with chlorambucil the response to therapy appeared to be a factor of prognostic significance. Patients who showed clinical and hematologic remission had a better prognostic outlook than those who showed only a partial response, while the worst prognosis was encountered in patients who did not respond at all. The five‐stage anatomico‐clinical classification system suggested appears to be the dominant prognostic factor and may thus serve as a guideline for therapeutic strategy. Cancer 40:855–864, 1977.