Background and Purpose: The aim of the present study was to validate ([ 1 8 F] fluoromisonidazole (FMISO) and [ 1 8 F]-2-fluoro-2'-deoxyglucose (FDG) positron emission tomography (PET) for determination of radiotherapeutically relevant hypoxia by the gold standard for measuring tissue oxygenation in human tumors, the computerized polarographic needle electrode system (pO 2 histography). Patients and Methods: Up to now, a total of 16 patients with a metastatic neck lymph node from a primary squamous carcinoma of the head and neck underwent pO 2 and PET measurements. Tumor tissue pO 2 was measured with polarographic needle electrodes using a pO 2 histograph (Eppendorf®). Under CT control, the needle electrode was placed in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO 2 readings, with values ≤ 2.5, ≤ 5.0, and ≤ 10.0 mmHg, as well as mean and median pO 2 were recorded. All PET studies were carried out using an ECAT EXACT 922/47® scanner with an axial field of view of 16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed 120 min after intravenous administration. The acquisition and reconstruction parameters were as follows: 15-min emission scanning and 4-min transmission scanning with 6 8 Ge rod sources. FDG PET of the lymph node metastasis was performed 68 ′ 11 min after intravenous administration, applying the whole-body tool with 8-min emission scanning and 4-min transmission scanning per bed position. Results: In order to detect possible relations between the different relevant polarographically measured parameters of tumor hypoxia and FMISO. PET data-based oxygenation values, the Pearson correlation coefficient was calculated. Average (r > 0.5) to high correlation (r > 0.7) was found between tumor-to-muscle ratio of FMISO after 2 h and parameters of hypoxic fraction (pO 2 readings with values ≤ 2.5, ≤ 5.0, and ≤ 10.0 mmHg as well as mean and median). No correlations could be shown between FDG PET parameters and polarographically determined tumor oxygenation status. Conclusion:Summarizing the FMISO uptake represents a global value for macroscopic tumor parts. As a noninvasive measurement this method seems highly feasible to evaluate the state of oxygenation in subjacent tumors.