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Objective To explore the clinical characteristics and prognosis of patients with different molecular subtypes of breast cancer with first-episode bone metastases. Methods The clinical data of 167 patients with first-episode bone metastasis of breast cancer were collected. According to the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and ki-67, patients were divided into Luminal A, Luminal B and HER-2 overexpression types and triple negative (TNBC) molecular subtypes. The clinical and prognostic characteristics of the four subtypes were analyzed. Results Among the 167 patients, 24 (14.37%) had Luminal A subtype, 102 (61.08%) had Luminal B subtype, 18 (10.78%) had overexpression HER-2 subtype and 23 (13.77%) TNBC subtype. The four subtypes were mostly invasive ductal carcinoma. In the pTNM staging, Luminal A was mainly stage I, and the other three types were mainly stage II-III. Luminal B is usually treated by radical mastectomy, and the other three types were usually treated by imitate radical surgery. There were no significant differences in menstrual status, lymph node metastasis, alkaline phosphatase (ALP) levels and breast cancer tumor marker levels, other distant metastases, skeletal-related events (SREs) and drug treatment modes between patients with four subtypes (P＞0.05). The median metastasis-free time of the four subtypes were 53, 34, 15 and 33 months, respectively (Log-rank χ²=10.592, P＜0.05). The median overall survival time was 90, 116, 63 and 61 months, respectively (Log-rank χ²=13.080, P＜0.01). The median survival time after bone metastasis was 35, 48, 23 and 18 months, respectively (Log-rank χ²=15.590, P＜0.01). The median metastasis-free time of patients with HER-2 overexpression was the shortest, followed by TNBC and Luminal B, and Luminal A was the longest. TNBC patients had the shortest overall survival time, followed by HER-2 overexpression and Luminal A, and Luminal B was the longest. Molecular subtypes, pTNM, targeted therapy, SREs and CA153 levels were independent factors influencing overall survival time in patients with first-episode bone metastasis of breast cancer (P＜0.05). The death risk in patients with HER- 2 overexpression and TNBC subtype were 2.799 and 2.306 times higher than that of Luminal A subtype. However, Luminal B had a 62% lower risk death than Luminal A. Conclusion Among the four molecular subtypes of breast cancer patients, patients with HER-2 overexpression and TNBC have poor prognosis. HER-2 overexpression is the first to have bone metastasis. [ABSTRACT FROM AUTHOR]