Background: Breast phyllodes tumors (BPT) have variable malignant potential, their histological classification remains insufficient for an accurate diagnosis.Objectives: We attempted to investigate CD10 (Cluster of differentiation 10) and EGFR (Epidermal growth factor receptor) expression in BPT in order to highlight their diagnostic and prognostic values.Methods: Eight patients with BPT are recruited from January 2014 to December 2020 and immunohistochemical assessment of CD10 and EGFR is realized.Results: Median age was 27±15.2, the mean tumor size was 9.63±10.21. Only malignant tumours showed expression for EGFR. Borderline and malignant tumors were CD10 positive. Patients overexpressing CD10 were postmenopausal with great tumor size, 25% of these were sarcomatous. Coexistence of CD10 and EGFR overexpression was found in 25% of cases and was associated with age (P=0.008), tumor size (P=0.030) and hitologic types (P=0.014). PC1 and PC2, were extracted, they accounted cumulatively for 94.7% of the variance of the data analysed, it suggests that patient’s age and histological type of tumor have significant association with CD10 and EGFR expression in BPT.Conclusions: EGFR and CD10 overexpressed combined proteins in phyllode tumors constitute, with histopathological parameters, an important prognostic factor as well as a promising potential targets.