Complete hydatidiform mole has a substantial risk of developing persistent gestational trophoblastic disease (PTD). Whether heterozygous complete moles, arising from dispermy, have a higher risk of such progression than their homozygous counterparts is controversial. In this study, the frequency of heterozygous XY complete mole in 93 consecutive cases of histologically proven complete moles managed in Hong Kong was assessed by the technique of chromosome in situ hybridization (CISH) using DNA probes specific for the short arm of the Y chromosome. The incidence of Y-chromosome positive complete mole in the groups of patients with spontaneous remissions and the group with PTD with or without metastasis was also compared. The presence of Y chromosome was identified in 6 of the 93 cases (6.5%), and this incidence fell within the range reported in the world literature. Of these 93 patients, 5 patients defaulted follow-up, while 10 patients developed PTD, with evidence of metastasis in 2 of them. The presence of Y chromosome was also assessed in another 15 patients with documented metastatic PTD. It was found that CISH signals for Y chromosome were identified in 5.1% (4/78) of complete moles with spontaneous remission and 8% (2/25) with PTD with or without metastasis (P > 0.05). Y chromosome was detected in 5.9% (1/17) of the complete moles that developed metastasis and in 5.8% (5/86) of the complete moles that either developed spontaneous remission or developed nonmetastatic PTD (P > 0.05). There is no correlation between the presence of Y chromosome and development of persistent gestational trophoblastic disease.