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Breast cancer is a leading cause of malignant mortality and morbidity in women worldwide. Histones are a family of linker proteins that are located in the nucleus. Histone H1.5 (HH1.5) is one of the families involved in the stabilization of chromatin structure and gene regulation. It shows altered expression and mutation in different types of human cancers.This study aimed to evaluate immunohistochemical expression of HH1.5 in invasive duct carcinoma in relation to pathologic parameters including histologic tumor grade, pathologic staging, and molecular subtyping.A retrospective study was carried out on 60 samples of invasive duct carcinoma, not otherwise specified (NOS). Immunohistochemical staining with the HH1.5 antibody was performed.HH1.5-positive expression was observed in 70% of the cases (42 of 60 cases). There was a statistically significant correlation between increased HH1.5-positive immunohistochemical expression and each of increased tumor size, increased lymph node positivity, and tumor histologic grade. There was a statistically significant association between the presence of lymphovascular invasion and a high HH1.5 score. Among estrogen receptor, progesterone receptor, and HER2/neu scores, only the Ki67 labeling index showed a significant positive correlation with the HH1.5 score. There was a highly significant difference between cases with different HH1.5 scores in terms of molecular types.The high expression of HH1.5 was associated with poor prognostic factors, including its differential expression in the carcinoma molecular types. Further characterization of the role of HH1.5 in breast carcinomas should be performed for the development of novel targeted therapies in this type of cancer.