The most important predictive criterion for patient survival in early-stage cutaneous melanoma is the status of the regional lymph nodes. Sentinel lymph node (SLN) biopsy provides valuable prognostic information in this regard. Age, sex, tumor thickness, Clark level, ulceration, lymphovascular invasion, mitotic index, and regression are some clinical and pathologic criteria that offer additional prognostic information. The recently developed antibody D2-40 reacts with endothelial cells of lymphatic vessels, and staining with D2-40 has identified lymphatic invasion (LI) in sections of primary melanomas. In this retrospective case series, Niakosari et al demonstrated that LI, as detected by D2-40 staining, was significantly associated with SLN positivity. Assessing LI by D2-40 staining and other clinicopathologic features may spare some patients the need for SLN biopsy.