We analysed 44 tissue samples from serous ovarian neoplasms of different malignant potential for Ki-ras mutations by denaturing gradient gel electrophoresis (DGGE) and direct sequencing after microdissection. Point mutations at codon 12 were found in 7 of 20 tumours of low malignant potential (LMP) (35%) and in 2 of 6 well-differentiated carcinomas (33%). In contrast, no mutations were detected in the 11 poorly differentiated ovarian carcinoma samples or in the 7 serous cystadenomas. The frequency of Ki-ras mutations in serous ovarian tumours seems to correlate with the malignant potential of the neoplasms. The data favour the hypothesis of a de novo development of poorly differentiated ovarian carcinomas and do not support an evolution from LMP tumours or well-differentiated carcinomas.