Hydatidiform moles have a high incidence rate in Asian countries like India. The molecular pathway leading to the pathogenesis and progression of hydatidiform moles is not yet understood. This study aimed to investigate the biological significance of Bcl-2 and p53 in complete hydatidiform moles (CHMs) as well as their influence on disease progression in the Indian population.Archival tissues from 35 patients with CHMs and 35 age-matched controls were examined for Bcl-2 and p53 expressions by immunohistochemistry.Bcl-2 was found to be immunolocalised in the cytoplasm of the syncytiotrophoblast, whereas p53 was observed in both the nucleus and cytoplasm of the syncytiotrophoblast and cytotrophoblasts. In CHMs, Bcl-2 was detected in 23 percent of patients and p53 nuclear expression, in 66 percent. A significant decrease in Bcl-2 expression was observed in CHMs (p-value is 0.015), and the down-regulation of Bcl-2 significantly correlated with higher nuclear expression of p53 (p-value is 0.002), indicating an inverse association between the two proteins (p-value is 0.0001). However, no correlation was found between the clinical progress of patients with CHMs and p53 and those with Bcl-2 protein expression.The current study demonstrated the significance of Bcl-2 and p53 in the pathogenesis of CHMs but did not reveal any association with disease progression.