Histologic distinction between complete hydatidiform moles and nonmolar abortuses in early pregnancy is often extremely difficult. This study details the chronologic changes that occur in normal placenta, especially in the villous stroma during gestational weeks 4 to 12 and compares the findings in 63 normal placentas and 73 early complete moles. Over time, the chorionic villi in normal placenta showed gradual but recognizable alterations, from basophilic/hypocellular and nonvascular stroma to basophilic/cellular stroma containing angiogenic cell cords (immature blood vessels), and then to loose, edematous/reticular stroma with mature blood vessels containing vascular lumina and hematopoietic components. A basophilic stroma, which was frequently seen in early complete moles, was a constant feature of chorionic villi younger than week 7 in normal placenta, but had disappeared after week 8, except in the newly branched sprouts. Trophoblastic proliferation was virtually unrecognizable in 59% of early complete moles, whereas circumferential trophoblastic sprouts during weeks 4 to 6 of normal placenta can be mistaken as that of complete moles. Few or no mature blood vessels and excessive stromal karyorrhexis are characteristic features of early complete moles, even in the absence of trophoblastic proliferation, but they are occasionally found in normal placenta younger than week 7. Although many features of normal and molar placenta were similar during the earliest weeks (5 to 6) including basophilic stroma, angiogenic cell cords (immature blood vessels), and often circumferential trophoblastic sprouts and proliferation, already by that time early moles showed significantly greater percentages of stromal cells undergoing karyorrhexis and apoptosis compared with normal placenta (37.6% vs. 5.4%). These results indicate the histologic features do exist early on in pregnancy to differentiate normal from molar pregnancy. Further, it points out that complete hydatidiform mole in addition to being disease of trophoblastic proliferation is also associated with defects in vasculogenesis and maturation of villous stromal constituents.