Objective: Investigation of the normal frequency of tetraploid metaphases in semidirect (STC) and cultured (LTC) chorionic villi. Methods: Fifty metaphases in STC- and in LTC-villi slides of 100 women of advanced maternal age were screened for tetraploidy. Results: Up to three tetraploid metaphases were encountered in 27% of the STC-villi preparations; the scores fitted a Poisson distribution. In all LTC-villi preparations tetraploid cells were seen; the scores fitted a log-Gaussian distribution. Conclusions: On the basis of these distributions, we propose a protocol for the management of tetraploid metaphases in chorionic villi, strongly reducing the number of prenatal follow-up investigations.