Objective: To explore the diagnostic efficacy of breast cancer by ultrasound elastography and contrast-enhanced ultrasound and its correlation with immunohistochemical indexes. Methods: Retrospective analysis of 134 patients of suspected single focus breast cancer who underwent ultrasound elastography and contrast-enhanced ultrasound were collected from February 2019 to March 2021. Contrast-enhanced ultrasound and ultrasound elastography were performed. The diagnostic efficacy of various diagnostic methods was analyzed with histopathological biopsy as the “gold standard”. At the same time, human epidermal growth factor receptor-2 (HER-2), estrogen receptor (ER), progesterone receptor (PR), and Ki-67 were detected, the correlations between ultrasonic parameters [time to peak (TTP), maximum enhancement (Emax) value] and immunohistochemical indexes were analyzed. Results: The diagnostic accuracy of contrast-enhanced ultrasound was 78.36%, the diagnostic accuracy of ultrasound elastography for breast cancer was 72.39%, and the combined diagnostic accuracy of the two was 94.03%. According to the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) of ultrasound elastography, contrast-enhanced ultrasound, and the two combined to predict breast cancer were 0.652, 0.743, and 0.928, respectively. At the same time, the Emax value [(144.47±22.13) kPa] and TTP levels [(17.58±2.11) s] of HER-2 positive expression were higher than those of negative expression; the levels of Emax value [(145.11±19.76) kPa] and TTP [(17.82±2.55) s] in patients with high Ki-67 expression were higher than those in patients with low Ki-67 expression (all P<0.05). By Spearman analysis, TTP was positively correlated with Ki-67. Conclusion: Contrast-enhanced ultrasound combined with elastography is more effective in the diagnosis of breast cancer, and the ultrasonic parameter TTP may be associated with Ki-67.