The organization of actin-containing microfilaments and vimentin- containing intermediate filaments has been investigated in B chronic lymphocytic leukemia (B-CLL), hairy cell leukemia (HCL), and normal B cells cultured in vitro under basal conditions and after induction with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In uninduced B-CLL cells, F-actin was predominantly associated with dot-shaped structures scattered over the ventral membrane representing spotty close contact adhesion sites analogous to ““podosomes” described in other cell types. On TPA induction, podosomes became clustered in sharply defined areas sitting in the cell center beneath the nucleus. In some cells, long actin-containing protrusions appeared. In HCL cells, F-actin was associated with thin microvilli responsible for the “hairy” appearance; occasional cells showed scattered podosomes. On TPA induction, HCL cells sprouted long dendritic processes rich in submembraneous F-actin, which made intertwined networks. Therefore, in both B-CLL and HCL cells, adhesion structures were present and the capacity for adhesion in vitro was marked, which might explain some peculiar clinical features of the diseases. Adhesion structures and adhesive properties never appeared in normal B cells. These data further support the notion that B-CLL and HCL, although clinically different, may share common biological features and suggest that in these disorders, cytoskeleton modifications may represent a hallmark of transformation.