<p>Epidermal Growth Factor Receptor (EGFR) signalling is thought to be involved in the pathogenesis of pemphigus vulgaris. The objective was to assess the cutaneous EGFR mRNA expression and serum soluble EGFR (sEGFR) levels among Pemphigus patients in comparison to the healthy controls. This was a cross-sectional study with a longitudinal follow up. Thirty patients with pemphigus vulgaris and 30 controls were recruited. We measured cutaneous EGFR mRNA expression and sEGFR serum levels in pemphigus vulgaris patients at baseline, at three- and six-months following treatment. There was a significant (<i>p</i> = 0.007) difference of the EGFR mRNA fold expression between cases (3.07 (IQR (Interquartile range) 0.76 to 13.20)) at baseline as compared to the controls (1.005 (Interquartile range (IQR) 0.63 to 2.30)). The median sEGFR levels were significantly (<i>p</i> &lt; 0.0001) higher in the cases (4.33 ng/ml (IQR 3.01 ng/ml to 9.33 ng/ml)) compared to controls (1.52 ng/ml (IQR 0.79 ng/ml to 2.75 ng/ml)) at the baseline. There was a significant positive correlations of EGFR mRNA expression (<i>r</i> = 0.47) and sEGFR levels (<i>r</i> = 0.46) with pemphigus disease activity. The limitation of the study was smaller sample size. EGFR gene expression and sEGFR levels are significantly increased in pemphigus vulgaris. They significantly correlate with disease activity and decrease with treatment.</p>