The objective of this study was to explore the protein expression pattern in normal endometrial mucosa (n = 5) and endometrial carcinoma (n = 15) of low (diploid) and high (aneuploid) malignancy potential by two-dimensional gel electrophoresis (2-DE). The specimens were evaluated for histopathologic subtype, stage and grade in relation to DNA ploidy. A match-set consisting of five samples from normal endometrium, eight diploid and seven aneuploid tumours was created. All the diploid and three of the aneuploid tumours were of endometrioid subtype, while the remaining four were of uterine seropapillary type. There were 192 protein spots differentiating diploid tumours from normal endometrium and 238 protein spots were separating aneuploid tumours from normal endometrium (p < 0.01). A cluster analysis based on 52 significantly deviating protein spots within the groups showed clustering and separation of the normal endometrium, diploid and aneuploid tumours. In conclusion this study showed significant differences in protein expression between normal endometrium and endometrial carcinoma as well as between endometrial carcinoma of low and high malignancy potential. In future studies these results may provide useful in finding new sensitive prognostic markers for endometrial cancer.