Mammography is the only modality proven to reduce mortality in breast cancer, and ultrasonography is a well-known adjunct to mammography screening. The Breast Imaging Reporting and Data System (BI-RADS) classification is a practical tool and is correlated with histopathology and combined use with triple assessment (examination, imaging, and biopsy) of palpable diagnostic cases. This study aimed to investigate the relationship between vascular endothelial growth factor (VEGF) expression and different grades of BI-RADS in breast cancer. Methods? Ninety-six patients with breast carcinoma were evaluated using BI-RADS by ultrasonography, mammography, and a combination of both modalities. In the combined imaging assessment, BI-RADS 1–4a grade was considered when the score of ultrasonography and mammography was lower than 4a, and BI-RADS 4b–5a grade was considered when the score of ultrasonography and mammography was higher than 4a. Immunohistochemical Ultra SensitiveTM S-P method was employed to evaluate the expression of VEGF in 96 patients. Fifty patients with benign breast disease were selected as the control group. The relationship between VEGF expression and different grades of BI-RADS and that between VEGF expression and other standard prognostic parameters associated with invasive breast cancer, such as size, grade, cancer stage, and metastasis were analyzed. ResuIts? The sensitivities of ultrasonography and mammography alone was 74.0% and 84.4%, respectively; However, the sensitivity of their combination increased to 90.6%. The positive rates of VEGF in invasive breast cancer BI-RADS 4b–5 (59/87, 67.8%) were higher than those in BI-RADS 4a (3/9, 33.3%, P< 0.05) and benign breast disease tissues (BI-RADS 1–4a, 11/50, 22.0%) (P< 0.05). There was a positive correlation between VEGF overexpression and BI-RADS 4b–5, histological grade (III), lymph node metastasis, and distant metastasis of invasive breast cancer. VEGF expression was not related to the age and size of the tumor in each group (P > 0.05). ConcIusion? There was a positive correlation between VEGF overexpression and BI-RADS 4b–5 grade. The overexpression of VEGF might be an important biological marker for the invasion and metastasis of breast cancer.