Objective To explore the potential value of conventional ultrasound combined with CA199 and CA125 in diagnosis of breast cancer. Methods 182 patients with breast masses were divided into breast cancer group (85 cases) and benign breast cancer group (97 cases), according to the pathological results. The patients were examined by conventional ultrasound and the serum levels of CA199 and CA125 were detected. The ROC working curve was used to analyze the effects of conventional ultrasound, CA199 and CA125 alone or in combination to detect breast cancer. Results Compared with benign breast tumors, the ultrasound of breast cancer was more often characterized by irregular shape, unclear boundary, small calcification, uneven internal echo and aspect ratio ≥1, and the difference were statistically significant (P＜0.05). Compared with patients with benign breast tumors, serum CA199 and CA125 levels were significantly higher in patients with breast cancer, and the difference were statistically significant (P＜0.05). The areas under the ROC curve of conventional ultrasound, CA199 and CA125 for breast cancer diagnosis were 0.755, 0.627 and 0.615, with sensitivity of 72.2%, 52.9% and 376%, specificity of 21.2%, 60.8% and 71.1%, respectively. The area under the ROC curve, sensitivity, specificity of the combined detection of the three indicators were 0.871, 83.2%, 65.3%respectively, and the diagnostic effect was better than that of the single indicator detection. Conclusion Conventional ultrasound, CA199 and CA125 detection have certain application value in the diagnosis of breast cancer, and the combined detection of the three can help improve the diagnostic efficiency.