In the t(15;17) translocation of acute promyelocytic leukemia (APL) at least three regions of the PML gene are involved in the reciprocal translocation between the PML and the RAR-alpha loci. The chimeric PML/RAR-alpha fusion transcripts can be demonstrated in all cases of APL, by a specific reverse-transcription PCR (RT-PCR). Previous studies found a correlation between expression of CD2 and involvement of the PML bcr3. In this study, we assessed this association in 43 children and adults with APL. A blind morphologic review of all smears was performed by four experienced hemopathologists who agreed the diagnosis of M3 vs M3v APL. CD2 expression on APL was detected by using different monoclonal antibodies (MoAbs) directed against specific CD2 epitopes by flow cytometry and in selected cases by Northern blot by the use of a specific CD2 cDNA probe. Nineteen of 43 cases displayed the typical microgranular features consistent with the diagnosis of M3v. Of these, 12 had the bcr3 breakpoint on chromosome 15, while seven had the bcr1 type. In 16 of the 19 patients, leukemic cells expressed both CD2 protein and the corresponding mRNA. Similarly, in the negative cases, Northern blot analysis failed to demonstrate the presence of specific mRNA. The remaining 24 patients, with the classic morphologic features of M3, were CD3 negative. These results point out that CD2 expression correlates with the FAB M3v and not with the PML breakpoints. During the course of all-trans retinoic treatment a down-modulation of CD2 expression was observed in three M3v cases. Overall, our findings might suggest a role of CD2 epitopes in the regulation of adhesion properties of APL blast cells.