The objectives of this study were to better our understanding of the carcinogenesis of gestational trophoblastic tumours and to investigate the possible presence of mutational alteration of the p53 tumour-suppressor gene in these tumours. Amplification-based direct DNA sequencing was performed on 14 hydatidiform moles, six invasive moles, eight choriocarcinomas and ten normal early placental tissues. No mutation in exons 5-8 was detected in any of these 38 tissue specimens. These results suggest that a mutation in p53 tumour suppressor either does not exist or is a very rare event in gestational trophoblastic tumours. The gestational trophoblastic tumours probably involve a tumour-suppressor gene other than p53 gene or may follow a completely different pathway to their malignant phenotype.