Knowledge of the nuclear DNA content of a hydatidiform mole is extremely useful in distinguishing a partial hydatidiform mole from a complete hydatidiform mole. Flow cytometry can be applied to both fresh or frozen tissue as well as to formalin-fixed, paraffin-embedded samples. Methodologies for extracting, staining, and analyzing nuclei are relatively simple and inexpensive, and results are accurate and reproducible. The vast majority of flow cytometers currently available or in use are more than adequate for distinguishing the large difference in nuclear DNA content between partial and complete hydatidiform moles, with sophisticated modeling programs and expensive equipment being unnecessary. We recommend that the DNA content of all hydropic placentas posing diagnostic dilemmas be analyzed by flow cytometry. When combined with clinical history and careful gross and microscopic examination, nuclear DNA content should serve as a very strong indicator of final diagnosis.