Background: Axillary staging (pN) is considered one of the main prognostic factors in breast cancer patients. However, the publication of the Z0011 study drastically reduced the number of surgical axillary dissections in a particular group of patients, limiting the prognostic information of axillary involvement only to the sentinel lymph node (SLN). Following the publication of the relationship between SLN total tumor load (TTL) and axillary involvement, this work aims to study a possible relationship between the former and recurrence risk and overall survival of breast cancer patients. Methods: clinicopathological and follow-up data were collected from 950 patients with breast cancer between 2009 and 2010 on whom SLN analysis was conducted by molecular methods (One Step Nucleic Acid Amplification). Results: TTL (defined as the sum CK19 mRNA copies in all SLN) correlates with disease free survival (HR, 1.08; p = 0.000004), with local recurrence free survival (HR = 1.07; p = 0.0014) and overall survival (HR: 1.08, p = 0.0032), clearly defining a low-risk group (TTL < 2.5E + 04 CK19 mRNA copies/uL) versus another high-risk group ( > 2.5E + 04 CK 19 mRNA copies/uL). The prognostic value of this variable is enhanced if other clinical and pathological criteria (tumor size, lymphovascular invasion, HER2, Ki67), grouped in a nomogram, are added. Conclusions: SLN TTL permits the differentiation between two patient groups in terms of disease-free survival and overall survival, independently of axillary staging (pN), tumor and age characteristics. This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed after sentinel node involvement.