Pancreatic cyst fluid (PCF) analysis provides valuable information in the preoperative evaluation of pancreatic cysts. Vascular endothelial growth factors (VEGF) and other proangiogenesis factors such a placental growth factor (PlGF) are promising biomarkers for identifying serous cystadenoma (SCA). VEGF-A has recently been reported as a SCA marker. We sought to assess the value of the VEGF-A/PlGF heterodimer as a potential biomarker of SCA in PCF.PCF was analyzed for VEGF/PlGF and 7 additional proangiogenic markers including VEGF-A, VEGF-C, VEGF-D, TEK tyrosine kinase, endothelial (TIE-2), soluble fms-like tyrosine kinase-1 (sFlt-1), PlGF, and basic fibroblast growth factor (bFGF). True-positive or false-negative results were determined by histological confirmation of SCA and false-positive or true-negative results with confirmation of a non-SCA cyst by either cytology or histology, elevated carcinoembryonic antigen ≥192 ng/mL, elevated amylase ≥5000 U/L, or detected KRAS/GNAS mutations.Forty-eight PCFs were analyzed; 1 was technically inadequate. Of the remaining 47, 3 (6%) contained measurable (>60 pg/mL) concentrations of VEGF/PlGF heterodimer: 1 pseudocyst, 1 cystic adenocarcinoma, and 1 SCA. Of 6 histologically confirmed SCAs, there was only 1 (17%) true positive. Six PCFs were not classifiable due to insufficient data, leaving 41 PCFs for performance calculations (33 true negative, 5 false negative, 1 true positive, and 2 false positive) yielding a sensitivity of 17% and specificity of 94%.VEGF/PlGF heterodimer is present in low concentrations in PCF and is an insensitive biomarker for SCA. Additional study is required to determine clinical utility of heterodimeric VEGF/PlGF in combination with other proangiogenic markers.