- Sentinel lymph nodes (SLNs) are examined for occult melanoma metastases for accurate staging to dictate optimal therapy. The aim of this case series was to discuss clinical challenges in SLN biopsy. Ten challenging cases were identified from over 700 melanoma patients with SLN biopsy for primary cutaneous melanoma at the Yale Cancer Center Melanoma Unit. These cases were complicated by issues of (1) visualization of SLN, (2) concurrent and topographically close melanomas, (3) aberrant lymphatic drainage outside standard basins, (4) altered lymphatic drainage secondary to surgery, and (5) access to SLN. This case series identifies complex clinical scenarios encountered with SLN biopsy that should be familiar to a surgeon involved in the surgical care of melanoma patients.