Objective To investigate the metastasis of non-sentinel lymph node (NSLN) in breast cancer patients with 1~2 positive axillary sentinel lymph nodes (SLN) and the related risk factors. Methods Clinicopathologic parameters of 383 breast cancer patients with 1~2 positive SLNs admitted in our hospital from 2016 to 2018 were collected and retrospectively studied. Univariate and multivariate analysis were used to explore the related predictors of NSLN metastasis. Results In the enrolled 383 patients, only 149 (38.9%) were observed with NSLN metastasis. Univariate analysis showed ultrasound axillary lymph node (ALN) status (P < 0.001), number of positive SLN (P=0.007), number of negative SLN (P < 0.001), number of SLN dissected (P < 0.001), metastatic rate of SLN (P < 0.001) and lymph-vascular invasion (LVI, P=0.003) were related with NSLN metastasis. Multivariate logistic regressive analysis indicated that ultrasound ALN status (P=0.001), number of negative SLN (P=0.019), metastatic rate of SLN (P=0.037), LVI (P=0.039) and HER2 over-expression (P=0.026) were the independent predictive factors of NSLN metastasis. Conclusion Ultrasound ALN status, number of negative SLN, metastatic rate of SLN, LVI and HER2 over-expression can be used as the independent predictive factors of NSLN metastasis. Attention should be paid to the clinicopathological characteristics when decision of avoiding axillary lymph node dissection in breast cancer patients with 1~2 positive SLNs.