We analyzed immunohistochemical expression of the p53 protein in 28 cases of human normal placentas, ranging from first-trimester to term, and 23 cases of trophoblastic diseases, including hydatidiform mole, invasive hydatidiform mole, and choriocarcinoma, using the labeled streptavidin-biotin (LSAB) method after heat-induced antigen retrieval. The positive reaction was restricted to the nuclei of cytotrophoblasts and intermediate trophoblasts, while the syncytiotrophoblasts showed rare immunolocalization. The majority of first-trimester (eight of 11) and second-trimester (four of five) placentas showed minimal (<5%,+) to mild (5–20%, 2+) positive reactions, whereas all cases of third-trimester and term placentas failed to stain. On the contrary, in the trophoblastic diseases, all cases of hydatiform mole evidenced varying degrees of staining from a minimal to a marked (>40%, 4+) reaction, and all cases of invasive hydatidiform mole showed minimal to moderate (20–40%, 3+) reactions. As a whole, the p53 staining was found to be more intense and higher in number in the trophoblasts of moles than in those of normal placentas. In the cases of choriocarcinoma, 50% (three of six) of the cases showed minimal to moderate staining. From our observation, it may be suggested that expression of the p53 protein could be correlated with proliferation and differentiation of the trophoblasts, especially in an early stage of pregnancy, and that expression of the p53 protein could also play a significant role in an early developmental stage of molar pregnancy.