Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the western hemisphere. It is characterized by a clonal proliferation of a population of CD5+ B lymphocytes that accumulate in the secondary lymphoid tissues, bone marrow, and blood. Some CLL patients remain free of symptoms for decades, whereas others rapidly become symptomatic or develop high-risk disease. Studying autophagy, which may modulate key protein expression and cell survival, may be important to the search for novel prognostic factors and molecules. Here, we applied flow cytometry technology to simultaneously detect autophagy protein LC3B with classical phenotypical markers used for the identification of tumoral CLL B cell clones. We found that two patients with progressing CLL showed increased expression of the autophagy protein LC3B, in addition to positive expression of CD38 and ZAP70 and unmutated status of IGHV. Our data suggest that activation of autophagy flux may correlate with CLL progression even before Ibrutinib treatment.