Classification of molar gestations into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and their differentiation from nonmolar hydropic abortions (HA) are traditionally accomplished by morphology alone. Sometimes, the process may be inaccurate or inconclusive especially in early diagnosed cases. With the availability of p57 KIP2 immunostaining (the product of a strongly paternally imprinted and maternally expressed gene), it may be possible to classify these lesions objectively. P57 KIP2 immunostaining is absent in CHM because it lacks a maternal genome, whereas PHM and HA show positive staining. The aims of this study were to evaluate the results of routine histopathological examination and p57 KIP2 immunoreactivity in a large series of molar and nonmolar HA in Tunisia, and to compare the accuracy of p57 KIP2 immunohistochemistry with that of nuclear DNA microsatellite polymorphism in identifying CHM. The immunohistochemical expression of p57 KIP2 protein was investigated in 220 specimens of first trimester hydropic abortuses, and it was compared with the original diagnosis based on morphology, including 132 CHM, 49 PHM, and 39 HA. Concordant results were obtained in 210 cases. In 9 of 10 cases with a discordant diagnosis (negative immunostaining in 8 cases morphologically diagnosed as PHM and one case diagnosed as HA), microsatellite DNA genotyping analysis agreed with the results of p57 KIP2 staining, confirming the diagnosis of CHM in these cases. Twenty cases of CHM with negative p57 KIP2 immunostaining were also analyzed by genotyping and indicated the absence of maternal contribution and the homozygosity for a single paternal allele in concordance with the androgenetic and monospermic origin of CHM in these cases. We confirm that for distinguishing CHM from its mimics, p57 KIP2 immunohistochemistry can be used as successfully as DNA microsatellite genotyping. However, molecular techniques are still required for the evaluation of some difficult cases with discordant positive p57 KIP2 staining.