AIM To determine the potential value of interphase cytogenetic and argyrophilic nucleolar organiser region (AgNOR) analyses in the diagnosis and classification of hydatidiform moles. METHODS Serial tissue sections from 37 hydatidiform moles, histologically classified as 11 complete and 15 partial, and from 11 hydropic abortuses were examined by in situ hybridisation using digoxigenin labelled probes specific for chromosomes 1, X, and Y, and a one step silver staining method. The percentages of diploid and triploid nuclei, and the mean number of AgNORs for each tissue were determined. RESULTS Interphase cytogenetics showed that eight of the 11 cases (73%) each of complete mole and hydropic abortus had diploid pattern and the three remaining cases (27%) of each group were triploid. Two of the triploid complete moles and one of the triploid hydropic abortuses were revised to partial moles and one remaining triploid complete mole was revised to hydropic abortus. Of the 15 partial moles, nine (60%) were triploid, and six (40%) were diploid. These diploid cases were revised to three complete moles and three hydropic abortuses. There was a significant difference (p < 0.0001) between the mean (SD) AgNOR count in partial mole (5.11 (0.91)) versus hydropic abortus (3.79 (0.90)) and complete mole (3.39 (0.97)). The total of 15 triploid cases showed a high mean AgNOR count of 5.24 (0.73). Also, after reclassification, eight of the nine partial moles (89%) had a mean AgNOR count of > or = 5. The results of analyses by the two methods were closely correlated. CONCLUSIONS Interphasecytogeneticanalysis using chromosome specific probes and AgNOR count provides a valuable approach for ploidy analysis in histological sections of hydatidiform moles and helps to resolve difficult cases.