POEMS syndrome and amyloidosis are rare plasma cell diseases that share common features, including polyneuropathy. The aim of this study was to investigate serum vascular endothelial growth factor (sVEGF) in patients with amyloidosis and to evaluate changes in response to treatment. Twenty‐five patients 17 primary light‐chain amyloidosis (AL‐A), 7 transthyretin amyloidosis (TTR‐A), 1 senile wild‐type TTR‐A were studied. sVEGF was analyzed by ELISA. Sera from 8 myeloma and 7 POEMS patients were also evaluated. The median sVEGF level was 420 pg/ml in AL‐A and 179 pg/ml in TTR‐A patients; this was significantly lower than in POEMS syndrome (median 2580 pg/ml, P = 0.0002 and 0.001, respectively). sVEGF of AL‐A patients showed no changes in response to treatment. sVEGF was not increased in amyloid patients regardless of neuropathy, and did not mirror the course of the disease. sVEGF should be tested in patients with overlapping and atypical clinical features. Muscle Nerve, 2011