Introduction. New therapeutic agents and biomarkers are needed for the treatment of aggressive endometrial cancer subtypes. Recently, HER2 has been recommended to be tested routinely in serous endometrial cancers. The aim of this study is to investigate the correlation between HER2 (ERBB2) protein overexpression and HER2 gene amplification and the relationship of HER2 gene amplification with prognosis in cancers with serous morphology. In addition, the concordance of HER2 testing in paired curettage and hysterectomy specimens is also investigated. Methods. Twenty five serous carcinomas and 8 carcinosarcomas with a serous morphology were included in the study. HER2 staining was performed on whole tissue sections by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). The system, which was proposed by Fader et al was used to evaluate the stainings. Results. Protein overexpression was detected in 27.3% (n = 9) of the cases, and gene amplification in 30.3% (n = 10). A significant positive correlation was found between the two methods (P < .0001). HER2 IHC revealed a heterogeneous staining pattern, such as intense complete membranous in solid areas, and basolateral in papillary and glandular areas. HER2 gene amplification was significantly associated with shorter overall (P = .005) and disease-free (P = .014) survival. The concordence of the results in curettage and hysterectomy specimens was also significantly high. Conclusion. HER2 is an important prognostic and predictive marker for endometrial cancers with serous morphology. HER2 IHC/ISH testing can be performed by using diagnostic curettage specimens which contain enough viable tumor cells. However, pathologists should be aware of the intratumoral heterogeneity for HER2 staining.