Over the past two decades, the sentinel lymph node biopsy (SLNB) based on sentinel node (SN) being the first lymph node that harbors metastases, revolutionized breast cancer management. SLNB presents much less morbidity when compared to radical axillary lymph node dissection (ALND) where all nodes are dissected irrespective of their metastatic involvement. The purpose of this study was to evaluate the effectiveness of SLNB by investigating whether the histological characteristics of the SNs identified using scintigraphy are predictive of the histological characteristics of the ALN basin. Methods: Fifty-five female breast cancer patients underwent lymphoscintigraphy and SLNB followed by ALND. The histological status of the SN/s was correlated to the histological status of the ALNs to determine whether the SN accurately stages the ALNs in breast cancer. Results: During surgery, SNs were successfully isolated in 52 out of 55 cases (94.5%) (range, 0 to 9). No SNs were identified in 3 cases (5.5%). Results demonstrate a significant association (p = 0.05) between the metastatic status of SNs and the corresponding ALNs in 42 out of 52 patients (80.8%), but with a high false-negative rate (FNR) of 37.5%. Conclusion: The findings of this study show that the sentinel node concept provides the benefits of SLNB in the majority of instances. However, further work is required in reducing the FNR. Once the effectiveness of SLNB as a staging technique is locally established, the need of ALND in SN-negative patients would be limited, thus improving the quality of life of Maltese breast cancer patients.