Background: Gestational trophoblastic disease are a group of benign and malignant entities, where the hydatidiform mole is the most common. p57 (KIP2) is the protein product of the paternally imprinted but maternally expressed gene. Because complete mole lack a maternal genomic component they are not expected to express imprinted genes that are normally expressed by the maternal allele and immunohistochemical analysis for p57(KIP2) has been shown to be a valuable tool in the diagnosis of a complete mole. p21 is a cell proliferation marker and the actively dividing cells show increased expression of p21 immunostaining. Based on this aim of our study is to evaluate the efficacy of immunohistochemical markers in differentiating partial hydatidiform mole from complete hydatidiform mole. Also to assess the role of immunohistochemical markers in assessing the malignant potential of molar pregnancies. Methodology: This is a retrospective and prospective study done at a tertiary care teaching hospital for a period of 2 years. A sample size of 52 cases are included in this study. All 52 cases were selected for this study and their representative formalin fixed paraffin embedded tissue samples were subjected to immunohistochemistry with a panel of 2 markers. Detailed history of the cases regarding age, symptoms, parity, radiological findings like ultrasonogram, history of previous pregnancy, details of gross characteristics were obtained. Result: 15 cases partial hydatidiform mole, 24 cases of complete hydatidiform mole, 11 cases of normal products of conception, 1 case of invasive mole and one case of choriocarcinoma were included in this study. The percentage of staining intensity of p57 is strong in 50%, weak in 28.8% and negative in 21.2%.In P21 -1+ staining was in 19 specimen, 2+ in 21 specimen and 3+ in 10 specimens. Conclusion: P57 is used as a potential marker in differentiating partial mole and hydropic abort us from complete mole, hence avoiding unnecessary DNA analysis. The over expression of p21 in complete mole, invasive mole and choriocarcinoma indicates its association with proliferative activity, hence it’s a useful marker to assess the malignant potential of molar pregnancy. P21 targeted therapy is available in the market, so it can be used as a therapeutic marker.