Cancer is caused by mutations appearing in genes regulating the division and death of cells. ErbB2 is a prime example for such an oncogene whose mutation and overexpression are commonly observed in several different human malignancies. Several cancer-associated mutations of ErbB2 are known, but the mechanism by which these mutations drive cancer formation remains unknown. We selected three such mutations (R143Q, R678Q, and V842I) together with two inactivating mutations (K753M, IC) and two other activating mutations (V659E, G778D). We generated cell lines in which either wild-type ErbB2 or one of its mutant versions was expressed together with the epidermal growth factor receptor (EGFR) and analyzed how these mutations affect the movement and clustering/dimerization of ErbB2 in the cell membrane. These biophysical characteristics are relevant to the biological properties of the protein since binding of an activating growth factor, EGF, to EGFR is known to bring about profound changes in the clustering and diffusion of ErbB2, the co-receptor of the EGFR. In agreement with literature data, we found that EGF-induced activation resulted in heterodimerization of EGFR with ErbB2 accompanied by retarded diffusion of ErbB2 in the cell membrane. On the contrary, activation of ErbB2 by mutations resulted in only a slight increase in ErbB2/EGFR dimerization, which was associated with their accelerated diffusion in the plasma membrane. We propose a model in which these pre-dimerized EGFR/ErbB2 clusters harboring mutationally-activated ErbB2 prime the signaling cascade without being already fully active, a conclusion supported by the lack of increased tyrosine phosphorylation in the preformed, mutationally-activated EGFR/ErbB2 dimers. The findings have been published in the Journal of Molecular Biology (https://doi.org/10.1016/j.jmb.2026.169770).