EFbB3 transactivation can make tumor cells resistance to ErbB1/ErbB2 targeting drugs. This Urges for a reliable method to determine cell surface ErbB3 levels, but ill our hands iodinated NRG1 beta is unstable and tends to Underestimate the number of ErhB3 receptors in a radio-receptor assay. Here we show by the use of a radio-labeled high affinity neuregulin Mutant NRG/YYDLL that ErbB3 levels can be determined in a reliable manner by Scatchard analysis. Furthermore we show by differential competition with Unlabeled NRG/YYDLL and betacellulin that the number of ErbB3 and ErbB4 receptors can be quantified separately oil Cultured human breast cancer cells. (c) 2008 Elsevier Inc. All rights reserved.