The presence of metastatic cells in the first draining lymph node is crucial for staging melanoma, traditionally treated by the removal of the regional nodal basin until few years ago. The results of some prospective studies of surgical strategy and the introduction of immunotherapy and targeted therapy has significantly changed clinical practice, reshaping the role of lymph node dissection. Single Lymph Node Biopsy (SLNB) is now used for accurate staging with less invasive surgery, aiding in identifying patients who may benefit from adjuvant therapy. The aim of this review is to enlighten the needs perceived during everyday clinical practice. Prognostication in melanoma is still a challenge, with serum lactate dehydrogenase (LDH) as the only biomarker. Elevated LDH levels correlate with worse outcomes in advanced melanoma.SLNB time and curative role are debated, with studies suggesting
that the timing of SLNB may influence outcomes and that SLNB has limitations in predicting mortality, especially in different age groups. The use of precision medicine tools like circulating tumour DNA (ctDNA) tests and the emerging role of neoadjuvant immune checkpoint inhibitors (ICI) are improving outcomes.
While SLNB still remains fundamental, further research is needed to identify which patients’ subgroups benefit the most from it.

Impact statement
This article challenges conventional melanoma staging by reintroducing single lymph node excision as a selective tool in modern practice. It proposes refined clinical criteria for its use, aiming to guide oncologists toward more personalized and pragmatic staging decisions in the era of precision oncology.