Complete hydatidiform moles (CHM) are the most common form of gestational trophoblastic disease. The prevalence rate is much higher in the state of Kerala, India, than in other parts of the world. The biology and role of growth factors are not fully understood in these tumors. In this study, we have immunohistochemically evaluated the expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) along with their receptor, epidermal growth factor receptor (EGFR), and we have related them to the proliferative activity in normal placenta and CHM using the expression of proliferating cell nuclear antigen (PCNA) as the marker of proliferation. The results suggest activation of both EGF-EGFR and TGF-α–EGFR autocrine pathways in both types of tissues, with a predominance of the TGF-α–EGFR autocrine pathway in CHM. This is especially so in the more aggressive cases of CHM, the persisting group of diseases.