The microanatomy of the dot-shaped, close-contact sites called podosomes and the mechanism of their formation have been investigated in vitro in the malignant lymphocytes of B chronic lymphocytic leukemia (B-CLL). In this paper the authors demonstrate that in B-CLL podosomes: (1) vinculin, talin, and beta 2 integrin (CD18) rings surround an F-actin core; (2) the beta 1 integrin is localized within the F-actin core; (3) the beta 3 integrin is not present. This distribution and organization of adhesion-related molecules appears to be unique to B-CLL lymphocytes, since it has not been observed in normal B cells. B-CLL adhesion and podosome formation are inhibited by the synthetic peptide GRGDSP that contains the Arg-Gly-Asp (RGD) sequence.