Purpose of Investigation: To investigate the presence of 15-lipoxygenase-1 (15-LOX-1) expression and its potential role in the pathogenesis of endometrial hyperplasia and endometrial adenocarcinomas. Materials and Methods: The authors investigated the presence of 15-LOX-l expression in samples from patients diagnosed with normal endometrium (n = 12), endometrial hyperplasia (n = 12), and endometrial cancer (n = 12). The immunohistochemical stainings were scored by three independent pathologists. A Western blot of 15-LOX-l determined the presence of protein expression in normal endometrium. A Kolmogorov-Smimov test was used to evaluate the data's distribution pattern. For pairwise comparisons of the combined scores between groups, the Mann-Whitney U test was used. Results: Based on the combined scores for 15-LOX-l expression, strong immunochemistry staining was observed in samples diagnosed with normal endometrium. There was a significant difference in 15-LOX-l expression between normal endometrium and endometrial adenocarcinoma (p = 0.03). Comparing tissues from normal endometrium and endometrial hyperplasia, there was a decline in the expression from normal endometrium to endometrial hyperplasia. However, the difference was not statistically significant. Conclusion: The present results show that a decrease of 15-LOX-l expression in the endometrial tumorigenesis process, starting from normal endometrium to hyperplasia and endometrial cancer, might be a trigger. Further studies are required to determine its potential use as a marker in a larger randomized multicenter study.