To assess the occurrence of high-risk human papillomavirus (HPV) infection and p53 alterations in minimal deviation adenocarcinoma (MDA) of the uterine cervix, paraffin sections were used to investigate the presence of HPVs 16 and 18 and p53 expression and mutation in six cases of MDA. By polymerase chain reaction, only one case was positive for HPV 16 and none was positive for HPV 18. By in situ polymerase chain reaction in the case positive for HPV 16, HPV 16 was detected in a low-grade squamous intraepithelial lesion overlying the MDA but not in the MDA itself. All of the MDAs were negative or only focally positive for pS3 by immuno-histochemistry. Our polymerase chain reaction DNA sequencing study failed to detect p53 mutation in exons 5 to 8 in those cases focally positive for p53 expression. These results suggest that MDA may be associated only occasionally with the high-risk HPVs or with p53 gene alterations.