Non-synonymous single nucleotide polymorphisms (nsSNPs) represent common genomic variations that alter protein sequence and function. Some nsSNPs affecting conserved amino acids have been reported to be associated with cancer susceptibility. Interestingly, Epidermal Growth Factor Receptor (EGFR) is commonly overexpressed and mutated in many cancers. In this study, we investigated the structural effect of three deleterious nsSNPs: rs17337451 (R962G), rs1140476 (R977C) and rs17290699 (H988P) within EGFR using computational tools. The modelled mutant dimers showed less stability than wild type EGFR dimer. Furthermore, we showed the important role of R962 and H988 residues in the EGFR dimer formation. We also report preliminary experimental data for SNP R977C suggesting that the variant C977 might confer greater risk for breast cancer. These results contribute to an improved understanding of the EGFR dimer stability and provide new elements for understanding the relationship between EGFR and cancer.