Molecular alterations in Epidermal growth factor receptor (EGFR) were investigated for the first time in molar placenta using protein expression, activation status, differential amplification status and mutational analysis. Invasive lesions showed upregulation of internal domain and downregulation of external domain with concomitantly high gene amplification and phosphorylation. Mutations distributed across different exons in non-invasive cases in contrast to single mutations restricted to exons 4 and 6 in invasive cases displayed a strong correlation to overexpression and phosphorylation status suggesting that higher copies of EGFR gene and mutations in exon 4&6 influence the invasive capacity of trophoblasts and can be used as a biomarker of invasion.