The optimal treatment of recurrent adrenocortical cancer (ACC) remains to be established since there are discrepant opinions on the value of repeat surgery. We did a retrospective analysis of the outcome of patients who were referred to our units from 1988 to 2006 for a recurrence of ACC, which occurred 283 years after radical removal of the tumor. In that period, the treatment policy of ACC recurrence differed among our units, since oncologists were more accustomed to use chemotherapy while endocrinologists recommended surgery more frequently. Patients were stratified in two groups according to the treatment received: group one included 33 patients (18 W, 15 M, aged 2164 years, median 38) who underwent repeat surgery, while group 2 included 16 patients (8 W, 8 M aged 1869 years, median 48) who were treated with chemotherapy (EDP + mitotane). Repeat surgery was radical in 25 patients while eight patients were left with residual ACC and were treated with the same chemotherapeutic regimen. The 2 groups did not differ as to demographic characteristics, ACC stage, Weiss score, use of adjuvant mitotane therapy and secreting status, while the disease-free survival (DFS) after the first operation was significantly longer in group 1 (19 mos (583)) than in group 2 (10 mos (244) (P=0.05). Survival after recurrence was significantly longer for group 1 (36 mos (8168)) than in group 2 (15.5 mos (6109) (P=0.001). In-group 1, 56% of patients are alive at the last follow-up, 27% of whom are free of disease, while only one patients is alive in group 2. DFS after repeat surgery was 22 mos (4132) in the 25 patients who had radical surgery. Such patients had the greatest survival when compared to patients in whom repeat surgery was incomplete or patients treated with chemotherapy alone (P<0.0001). The present data suggests that re-operation for recurrence of ACC is beneficial when a complete removal of tumor can be attained, while debulking does not give any advantage in comparison to medical therapy. Even if this is a retrospective analysis, the patients treated surgically or medically were rather well matched for the most important prognostic factors; however, we cannot exclude selection of less aggressive ACCs in group 1. Notwithstanding these limitations, these data are of interest because they show that surgical treatment of recurrence is worth doing also in some patients with advanced ACCs. An extended DFS following primary surgery may be an important factor for proper selection of patients.