Positron emission tomography (PET) is a an important technology for detection and staging of breast cancer. The method is based upon assessment of glucose metabolism using the 18F-fluorodeoxyglucose (18F-FDG) as glucose analog. A strong variability of 18F-FDG uptake by breast cancer tissue has been reported, the reason for which is not fully understood but may involve vascular density and integrity. A 936C>T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels and breast cancer risk. To analyze the role of this polymorphism for 18F-FDG uptake in breast cancer patients, we determined the VEGF genotype in 37 patients in whom PET was performed for detection of metastases. An 18F-FDG uptake score of 1 (low uptake), 2 (medium uptake) or 3 (high uptake) was assigned to each patient. VEGF CC, CT and TT genotypes were found in 28, 8 and 1 patient. Uptake score of 1 was found in three patients, score 2 in 12 patients and score 3 in 22 patients. VEGF genotype was significantly associated with FDG uptake score (chi2 test, p=0.007). The number of 936-T alleles correlated with a lower 18F-FDG uptake score (Spearman correlation test, p=0.032). In the present study the common VEGF 936C>T polymorphisms had a major impact on 18F-FDG uptake in breast cancer patients. If this result can be confirmed in following studies, it might have strong relevance for the use of PET as diagnostic tool.