Objective: To compare the clinicopathological characteristics of second primary lung cancer following breast cancer and lung metastases from breast cancer, and then to analyze the risk factors in breast cancer patients with second primary lung tumor. Methods: Clinical data of 55 breast cancer patients with second primary lung tumor and 205 breast cancer patients with solitary pulmonary metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were retrospectively analyzed. The risk factors of primary lung cancer following breast cancer were analyzed using logistic regression model. Results: Second primary lung cancer in patients with first breast cancer accounted for approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and 0.84%(55/6 580) of all breast cancer patients. The median intervals between the diagnosis of second primary lung cancer or lung metastasis and first breast cancer were 52 months and 42 months, respectively. These two groups showed significant difference between age, time interval between diagnoses, breast tumor size, axillary lymph node metastasis, estrogen receptor, molecular subtype (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A multivariate logistic regression model confirmed that age (OR=1.088, P<0.001), breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460, P=0.004) were all independent factors for second primary lung cancer. Conclusions For isolated pulmonary nodules in patients with breast cancer, especially for those with elder age, larger tumor size and radiotherapy history, we should distinguish the second primary lung cancer from pulmonary metastasis. The treatment regimen for lung metastasis and primary lung cancer in patients with breast cancer are entirely distinct. The timely histopathology examinations for pulmonary nodes in patients with breast cancer are recommended.