Axillary lymph node dissection (ALND) is the standard of care for nodal staging of patients with invasive breast cancer. Due to significant somatic and psychological side effects, replacement of ALND with less invasive techniques is desirable. The goal of this study was to evaluate the clinical usefulness of axillary lymph node (ALN) staging by means of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in breast cancer patients qualifying for sentinel lymph node biopsy (SLNB). FDG-PET was performed within 1 week before surgery in 24 clinically node-negative breast cancer patients with tumors smaller than 3 cm. Sentinel lymph nodes (SLNs) were identified by preoperative lymphoscintigraphy following peritumoral technetium 99m-labeled colloid albumin injection, and by intraoperative gamma detector and blue dye localization. Following SLNB, a standard ALND was performed. Serial sectioning and immunohistochemistry of the SLN as well as standard histologic examination of the non-SLN was performed. FDG-PET detected all primary breast cancers. Staging of ALNs by PET was accurate in 15 of 24 patients (62.5%), whereas PET staging was false negative in 8 of 10 node-positive patients and false-positive in 1 patient. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for nodal status was 20%, 93%, 67%, and 62%, respectively. The mean diameter of false-negative ALN metastases was 7.5 mm (range 1-15 mm). Lymph node staging using FDG-PET is not accurate enough in clinically node-negative patients with breast cancer qualifying for SLNB and should not be used for this purpose.