Abstract Background The omission of axillary dissection for positive sentinel-node breast cancer is considered the standard treatment for patients who undergo breast conserving surgery and radiation therapy, according to the results of ACOSOG-Z0011 and AMAROS trials. On the other hand, some surgeons still think that the surgical stress of axillary dissection is minimal, and dissection is permitted. Furthermore, Z0011 contains several problems, such as insufficient number of entry cases and lack of radiation field unity. Thus, we planned a prospective trial to confirm the safety of omitting axillary dissection in patients with breast cancer and positive sentinel nodes. Trial design This is a single arm, confirmation study of three medical centers. Prior to surgery, informed consent is obtained, and patients are registered primarily. After surgery, patients with 1 to 2 positive sentinel nodes, for whom axillary dissection was omitted, are finally included in this trial at final registration. Eligibility criteria Patients with histologically-diagnosed breast cancer, Tis–2, N0 based on a core needle biopsy, will be included in this trial. Eligible patients must be between 20 and 80 years of age, with a performance status of 0–2 and adequate organ function. They must not have undergone any prior operation, radiation therapy, chemotherapy, endocrine therapy, or immunotherapy. Specific aims The primary endpoint is 5-year (y) axillary recurrence rate. Secondary endpoints are 5-y overall survival, 5-y recurrence-free survival, 5-y local recurrence-free survival, the rate of upper-limb lymphedema, quality of life, and comparison of axillary recurrence rates between patients with two or more dissected nodes and those with only one positive node. Statistical methods The expected rate of axillary recurrence is 2.0%, and non-inferiority is defined as an axillary recurrence lesser than or equal to 5% in the axillary radiotherapy group. The sample size was calculated with a study power of 80% and type I error of 10% (two-sided). The required number of patients is estimated to be 189. Present and target accrual Patient accrual from the three medical centers was initiated in July 2016. We plan to enroll a total of 189 patients at final registration in this trial. Citation Format: Jibiki N, Hirano A, Ochi T, Sakamoto A, Horiuchi K, Noguchi E, Omi Y, Ogura K, Inoue H, Kamio T, Naritaka Y, Fujibayashi M, Hiroshima K, Nagashima Y, Sakai S, Karasawa K, Okamoto T. A confirmation study of omitting axillary dissection in patients with breast cancer and positive sentinel nodes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-02-01.