Bcl-2/IgH rearrangement is the molecular hallmark of follicular lymphoma (FL) which is present in 70-90% of the cases at diagnosis. The clinical significance of this feature is controversial. The aim of this study was to analyze the bcl-2/IgH rearrangement by means of a PCR technique, and to correlate molecular findings with clinical characteristics and outcome. Sixty-nine patients (median age, 53 years; male/female ratio: 35/34) diagnosed with FL in a single institution were included in the study. A total of 77 DNA samples were analyzed, 54 were obtained from lymph node biopsy and 23 from peripheral blood or bone marrow. Bcl-2/IgH rearrangement was assessed for both the major breakpoint region (MBR) and the minor cluster region (mcr) breakpoints by a PCR technique. Thirty-nine out of sixty patients (65%) with assessable samples were found to have a bcl-2/IgH rearrangement in the MBR breakpoint, whereas bcl-2/IgH rearrangement in mcr was observed in one patient (2%) and no rearrangement at MBR or mcr in the remaining 20 patients (33%). Regarding the initial characteristics, patients with bcl-2/IgH rearrangements at MBR or mcr were younger (<65 years) than those with no rearrangement at these sites (p = 0.0001). No differences were found according to bcl-2/IgH rearrangement in terms of complete response rate, time to treatment failure and overall survival. In our series bcl-2/IgH rearrangement at MBR or mcr, which was found in 67% of the patients, was not correlated with response to treatment, survival nor time-to-treatment-failure.