To prospectively evaluate the accuracy of integrated [11C]choline-PET/CT in the diagnosis of lymph-node recurrence in prostate cancer patients with biochemical failure after surgery.Since October 2002, 25 patients with biochemical recurrence (median PSA: 1.98ng/ml), based on evidence of lymph-node metastases on [11C]choline-PET/CT scan (21 cases) or conventional imaging (4 cases), were scheduled for either bilateral pelvic (12 cases) or both pelvic and retroperitoneal lymph-node dissection (13 patients).Sixty-three nodal sites were evaluated histologically. The mean number of nodes removed and positive nodes were 21.92±16.91 (range: 4–74) and 8.84±9.65 (range: 1–31), respectively. Of the four patients with negative [11C]choline-PET/CT and positive magnetic resonance, none had nodal metastases. Nineteen of the 21 patients (90%) with positive [11C]choline-PET/CT had nodal metastases of prostate adenocarcinoma at histologic evaluation. A lesion-based analysis showed that [11C]choline-PET/CT sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 64%, 90%, 86%, 72%, and 77%, respectively. The mean maximum diameter of true positive metastases was larger than false-negative ones (15.0 vs. 6.3mm; p=0.0004).[11C]Choline-PET/CT is an accurate diagnostic tool for the detection of lymph-node metastases of recurrent prostate cancer. The low negative predictive value seems to depend on the limited capability of [11C]choline-PET/CT to detect microscopic lesions. The high positive predictive value, even with low PSA values, provides a basis for further treatment decisions.