High-grade malignancies are the leading cause of death from gynecological tumors. Unfortunately, no efficient screening method is available for these tumors. In this paper we report the results of a pilot study based on the frequency of TP53 mutations in these cancers. Mucus from the cervix of 32 hysterectomy specimens with no grossly visible cervical or serosal involvement were included in this study. TP53 exons 5-9 mutations were screened for mutations using single strand conformation polymorphism (SSCP). Immunostain for p53 protein was performed in all fallopian tubes and in a sample from the tumors that were identified prospectively. A total of 32 cases including 19 malignant, and 13 benign cases were included. P53 immunostain was positive in only 5 cases including 3 high grade malignant tumors and 2 precancerous lesions (serous tubal intraepithelial lesion or p53 signature) in the fallopian tubes. A TP53 mutation band pattern was detected by SSCP in 2/3 and 2/2 cases respectively. Twenty-seven cases were negative for p53 imunostain, 4 of which were positive for TP53 mutation by SSCP including 3 low-grade malignancies. The results of this study provide evidence that DNA from precursor lesions of high grade ovarian, fallopian tube and endometrial carcinomas can be detected in cervical mucus. Further studies using different markers, in preoperative setting and large scale screening studies will determine the utility of using cervical mucus to screen for gynecological malignancies.