Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.