ABSTRACT: The Oncotype DX 21-gene test can be used to predict chemotherapy efficacy in patients with estrogen receptor (ER)-positive and HER2-negative breast cancer; however, the data on the 21-gene recurrence score (RS) for mucinous breast carcinoma (MBC) are limited. The present study aimed to evaluate the distribution pattern and clinical value of the 21-gene RS in patients with MBC. A total of 38 pure MBC (PMBC) and 11 mixed MBC (MMBC) cases were retrospectively analyzed, and a total of 29 ER-positive and HER2-negative MBCs underwent the Oncotype DX 21-gene test. There were no statistically significant differences between the PMBCs and MMBCs in age, tumor size and molecular subtype; however, patients with MMBC showed a significantly higher incidence rate of nodal metastases compared with that in patients with PMBC (72.7 vs. 16.2%, respectively). Following surgery, 87.8 and 59.2% of the enrolled patients received endocrine therapy and chemotherapy, respectively. With a median follow-up of 65.6 months, the 5-year disease-free survival and overall survival rates were 97.0 and 100.0%, respectively. The 21-gene test revealed that the proportions of patients with MBC categorized into low (RS <18), intermediate (RS ≥18-30) and high (RS ≥30) risk groups were 51.7, 44.8 and 3.5%, respectively, and there was no statistically significant difference between the PMBC and MMBC cases. Notably, among the genes in the 21-gene RS testing, the expression levels of cathepsin V, progesterone receptor (PR) and CD68 were significantly higher in the PMBC group compared with that in the MMBC group. In conclusion, the current study demonstrated that patients with MBC had a favorable prognosis, and both PMBC and MMBC cases had a low- and intermediate-risk RS, which suggests that a considerable proportion of patients may be able to avoid chemotherapy. In addition, the high expression level of PR, based on the 21-gene test in PMBCs, indicated that they may have a more favorable response to endocrine therapy than MMBCs.