The main objective of the present study was to estimate the levels of soluble CD44 in cervical cancer patients by determining whether it consistently discriminates the carcinoma of the cervix from early or premalignant stage of the cervical cancer. Serum concentrations of sCD44s in cervical cancer patients were determined by an enzyme-linked immunosorbent assay from serum of 50 cases of cervical cancer patients and 50 cases of suspected patients with premalignant disease of cervical intraepithelial neoplasia. The sensitivity and specificity of the test for differentiating carcinoma of the cervix from premalignant stage were evaluated by plotting receiver operating characteristic (ROC) curve. Significant increase in the levels of soluble CD44 was observed in cervical cancer patients (664.80 ± 26.58 ng/ml), when compared to healthy (P < 0.001) and suspected (P < 0.05) or premalignant cases (275.19 ± 24.39 and 514.33 ± 54.57 ng/ml, respectively). High-grade squamous intraepithelial lesions, adenocarcinoma in situ and premalignance with dysplasia show significant (P < 0.001) increase in the concentration of soluble CD44 levels when compared to other types. A ROC curve was plotted and estimated the threshold value as 633.11 ng/ml. In conclusion, the data indicated an up-regulation of soluble CD44 protein which detect and differentiates the cervical carcinoma from premalignant cases with 62.6 % sensitivity.