Introduction: The use of neoadjuvant therapy (NAT) has been showing an incraesing tendency in the treatment of locally advanced breast cancer. The evaluation of residual cancer could be performed by Residual Cancer Burden (RCB) calculator. The prognostic system takes the two largest diameters of the tumor, the cellularity, the amount of in situ carcinoma, the number of metastatic lymph nodes, and the size of the largest metastatic deposit into account. The aim of our study was to examine the reproducibility of RCB in NAT treated patients. Methods: Patients who were treated with NAT and had resection specimens between 2018 and 2021 were selected. Histological examination was performed by five pathologists. After assessment of the examined variables, RCB points and RCB classes were defined. For statistical analysis, interclass correlation was used (SPSS Statistics V.22.0 software). Results: Altogether 100 patients were included in our retrospective, cohort study (average age: 57 years). In two-thirds of the cases, third generation chemotherapy was used, and mastectomy was performed. Significant concordance was found in the two largest diameters of the tumor (coefficients, 0.984 and 0.973), the cellularity (coefficient, 0.970), and the largest metastatic deposit (coefficient, 0.998). Although the amount of in situ carcinoma proved to be the least reproducible factor, it resulted in almost 90% of agreement (coefficient, 0.873). Regarding RCB points and classes, similar results were observed (coefficients, 0.989 and 0.960). Conclusions: Significant agreement was observed between examiners based on almost all RCB parameters, points, and classes, reflecting the optimal reproducibility of RCB. Therefore, we recommend the use of the calculator in routine histopathological reports in NAT cases.