Background: In Vietnam and Italy, breast cancer (BC) occurs in women more frequently than any other cancer. Vietnam has a substantially lower incidence of breast cancer than Italy, but a higher mortality rate. Most Vietnamese patients present to the hospital with severe tumors at the late stages of diagnosis. The purpose of this study was to compare clinicopathologic features, biomarkers, and subtypes of BC between Vietnamese women and Italian ones. Methods: The sample was collected from all Vietnamese patients undergoing surgery with the diagnosis of primary invasive breast carcinoma in Hue Central Hospital as well as Hue University Hospital in Vietnam during 1 year from April 2016 to April 2017, and from the same category of women in Sassari University Hospital, Italy during the year 2016. The study parameters in both groups consisted of age at diagnosis, tumor size, histologic grade, histologic type, axillary node status, stages of diagnosis, biomarkers (Estrogen Receptor - ER, Progesterone Receptor - PR, Ki-67 cell proliferation marker - Ki-67, Human epidermal growth factor receptor 2 - HER2), and molecular subtypes of BC. Results: 323 patients were collected in total (235 from Sassari, Italy, and 88 from Thua Thien - Hue province, Vietnam). Vietnamese patients were diagnosed at a younger age than Italian patients, at just 52.5 on average, while the figure for Italian was 62. The Vietnamese BC patients also had a bigger tumor in size, higher grade, more axillary node positivity as well as a later stage of disease in comparison with Italian ones. The proportion of ER-positive was higher in the Italian group than that in Vietnam (88.1 vs 55.7%). The high Ki-67 expression prevalence was significantly higher in Vietnamese patients compared with Italian (81.8 vs 45.1%). The HER2-positive rate in Vietnam was 33%, higher than that in Italy (8.1%). Histologic grade and cell proliferation index Ki-67 were significantly correlated with HER2 positivity in both groups. Conclusions: Vietnamese patients demonstrated more aggressive tumor features and worse prognostic biomarkers than Italian patients. The prevalence of HER2 positive and high Ki-67 expression in Vietnamese patients was considerably higher than in Italian patients. The remarkable differences in clinicopathological characteristics between the two populations suggest the diversity of biological tumor, ethnicity, and environment as well as the effectiveness of the screening program.