Introduction <p>Cancer of the cervix is one of the leading causes of death in reproductive-age women around the world. The most common etiological factor is the Human papillomavirus (HPV). This prospective study was designed to analyse the HER-2/neu expression in premalignant and malignant lesions of the uterine cervix and to correlate the histomorphology of cervical lesions with HER-2/neu in cervical lesions.</p> Materials and Methods <p>This 1-year prospective study includes 58 confirmed cases of premalignant and malignant cervical lesions. DAKO Polyclonal Rabbit Anti-Human c-erbB-2 oncoprotein was utilised. IHC was performed using the usual streptavidin–biotin peroxidase method. The degree of HER-2/neu expression was rated using the 2014 ASCO/CAP HER-2/neu reporting standards.</p> Results <p>Out of a total of 58 cases, HER-2/neu expression scores were 0 in 67.24% {28 Cervical Intraepithelial Neoplasia (CIN), 11 Squamous Cell Carcinoma (SCC)}, + 1 in 10.34%, (02 CIN and 4 of SCC) + 2 in 10.34% [05 SCC and 01 adenocarcinoma (ADCA)] and + 3 in 12.06% (04 SCC, 02 ADCA and 1 adenosquamous cell carcinoma (AD-SQ)]. The rate of HER-2/neu over-expression in malignant (29.31%) cases was more significant than in premalignant (6.66%) (<i>p</i> = 0.01), and expression scores were higher (+ 2 and + 3) in 20.68% of malignant compared to none of the premalignant cases (<i>p</i> = 0.01). All ADCA cases had significantly higher HER-2/neu scores (+ 2 and + 3) than SCC (<i>p</i>&#xa0;=&#xa0;0.01). HER-2/neu expression was statistically substantially greater in malignant patients with Moderately Differentiated (MD) + Poorly Differentiated (PD) 84.62% versus Well Differentiated (WD) 15.38% (<i>p</i> = 0.074).</p> Conclusion <p>According to the findings, HER-2/neu expression is lower in cervical lesions. However, our results show that the HER-2/neu expression rate increases progressively when lesions advance from well to poorly differentiated.</p>