Background and purpose <p>A subset of newly diagnosed prostate cancer patients harbor occult lymph node metastases (LNM) that are not detected by standard [⁶⁸&#xa0;Ga]Ga-PSMA-11 PET/CT, leading to potential understaging and suboptimal treatment planning. This study investigates the performance of [¹⁸F]FDG PET/CT as a secondary imaging tool to identify these PSMA-negative LNM.</p> Methodology <p>We retrospectively analyzed 133 patients with newly diagnosed prostate cancer who were considered node-negative (miN0) by [⁶⁸&#xa0;Ga]Ga-PSMA-11 PET. All patients underwent a subsequent [¹⁸F]FDG PET/CT scan followed by radical prostatectomy and extended pelvic lymph node dissection (ePLND), with histopathology serving as the reference standard. The diagnostic efficacy of [¹⁸F]FDG PET/CT was benchmarked against the Briganti 2019 nomogram.</p> Results <p>Post-surgical pathology confirmed occult LNM in 11.3% (15/133) of patients. On a patient-based analysis, [¹⁸F]FDG PET/CT demonstrated a sensitivity of 73.3% and a specificity of 94.9% for detecting these occult LNM. This performance was significantly superior to the Briganti 2019 nomogram, with an area under the curve of 0.841 versus 0.621 (<i>P</i> &lt; 0.001). Notably, multivariate analysis revealed that a lower serum prostate-specific antigen (PSA) level was an independent predictor of [¹⁸F]FDG-positive LNM (<i>P</i> = 0.013).</p> Conclusions <p>In patients with newly diagnosed prostate cancer deemed node-negative by [⁶⁸&#xa0;Ga]Ga-PSMA-11 PET, supplementary [¹⁸F]FDG PET/CT can identify a significant proportion of occult LNM missed by initial staging. Our findings suggest that this dual-tracer approach may be particularly beneficial for patients with lower serum PSA levels, potentially improving risk stratification and selection for ePLND.</p>