3,4-Dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) positron emission tomography (PET) is sensitive for identifying primary brain tumors. However, increased FDOPA uptake has been reported in pseudotumoral brain lesions. Our aim was to analyse FDOPA-PET in patients with pseudotumoral brain lesions and to compare them with patients with brain tumors.We retrospectively analysed consecutively recruited patients with suspected primary brain tumor (based on clinical and magnetic resonance imaging findings) referred for FDOPA-PET in our centre between November 2013 and June 2019 (n = 74). FDOPA-PET parameters (maximum and mean lesion standardised uptake values [SUV] and ratios comparing lesion with different background uptake SUV) and thresholds were evaluated to determine which offered optimal discrimination between pseudotumoral and tumoral lesions.Overlapping PET values were observed between pseudotumoral (n = 26) and tumoral (n = 48) lesion, particularly for low-grade tumors. Based on receiver operating characteristic (ROC) analyses, the optimal PET parameters to discriminate pseudotumoral from tumoral lesions were SUVmax lesion/basal ganglia, SUVmax lesion/grey matter, SUVmean lesion/grey matter, and SUVmax lesion/mirror area in contralateral hemisphere (all ratios showing area under the curve [AUC] 0.85, 95% CI). The narrowest 95% sensitivity-95% specificity window was observed for SUVmax lesion/basal ganglia ratio, with ratio values of 0.79 and 1.35 corresponding to 95% sensitivity and 95% specificity, respectively.FDOPA-PET uptake should be interpreted with caution in patients with suspected primary brain tumor, especially in patients showing low or intermediate SUV values and ratios. CLINICAL TRIAL REGISTRATION-URL: https://www.clinicaltrials.gov . Unique identifier: NCT04306484.