We have found for the first time that Tspan5 upregulation facilitates the morphological conversion of tumour cells from the epithelial‐like to more mesenchymal‐like phenotypes, increases the expression of F‐actin and actin cytoskeleton rearrangement from the actin bundles underneath cell membranes to dynamic structures of actin fibres throughout the cells, reduces the expression of E‐cadherin (an important caretaker for the epithelial phenotype) and increases the expression of N‐cadherin and vimentin (two goalkeepers for the mesenchymal phenotype). This evidence concerns the gene TSPAN5 and neoplasm.