Fluorescent in situ hybridization (FISH) for HER2 performed on paraffin-embedded tissue samples and immunohistochemical analysis for p57 may be useful ancillary studies to aid in the diagnosis and classification of hydatidiform moles (HMs). HER2 FISH was validated against 24 paraffin-embedded sections of HMs and hydropic abortions and showed an 85% concordance rate. A morphologic assessment based on 44 cases showed 25% disagreement between original and consensus diagnosis based on H&E-stained slides, all of which involved the differential diagnosis of partial mole and hydropic abortion. Immunohistochemical analysis for p57 and HER2 FISH were performed, and a final diagnosis was assigned by using the results from all ancillary studies. p57 staining was absent in 11 of 13 complete moles, and HER2 was triploid in 8 of 10 partial moles .HER2 FISH and immunohistochemical analysis for p57 are useful ancillary techniques in the evaluation of HM, especially when triploid content is seen.