Experimental evidence for the existence of gas phase isomers in monolayer protected noble metal clusters is presented, taking Ag44(SR)30 (SR = 4-fluorothiophenol, p-mercaptobenzoic acid) and Ag29(BDT)12 (BDT: benzene dithiol) clusters as examples which do not show any isomeric structures in their crystals. Electrospray ionization coupled with ion mobility separation allowed for the identification of multiple isomers of Ag44SR30 cluster in its 3- and 4- charge states, their most abundant gas phase ions. Ag29(BDT)12 showed isomerism in its common 3- charge state. Isomerism is likely to be due to different types of ligand orientations in the staples leading to changes in the overall size and shape of the cluster ions, which was further confirmed by density functional theory calculations on Ag44(FTP)304-. No isomers were seen in the ions of the well-known cluster, Au25SR18 (SR = phenylethanethiol, dodecanethiol, and butanethiol). © 2017 American Chemical Society.