A retrospective survey was performed in 205 cases of gestational trophoblastic neoplasia with the use of routine tissue sections and quinacrine stain after hydrolysis and pronase pretreatment. The method allows scoring of nuclei simultaneously for either Y chromatin or X chromatin (Barr body) and has proved to be a valid test for sex assignment in tissue sections. Y-chromatin positivity (indicating gamete heterozygosity) was found in 16 of 182 cases (9%) of hydatidiform mole, two of four cases (50%) of invasive mole, and 14 of 19 cases (74%) of choriocarcinoma. The cytogenetic literature of 173 cases of complete hydatidiform mole indicates 8.1% have been 46,XY. Our unexpectedly high incidence of Y chromatin in malignant gestational trophoblastic neoplasia would suggest that homozygosity for a recessive mutant oncogene is not an important factor in pathogenesis of choriocarcinoma. The partial allograft theory of pathogenesis after nonmolar antecedents with attendant diminished host immunoreactivity remains a plausible consideration.