Melanoma exerts immune suppressive effects to facilitate tumor progression and metastatic spread. We studied these effects on dendritic cell (DC) and T-cell subsets in 36 melanoma sentinel lymph nodes (SLN) from 28 stage I-III melanoma patients and determined their clinical significance. Four conventional DC subsets; plasmacytoid DCs; and CD4+, CD8+, and regulatory T cells (Tregs) were analyzed by flow cytometry. We correlated these data to clinical parameters and determined their effect on local and distant melanoma recurrence, with a median follow-up of 75 months. In stage I and II melanoma, increased Breslow thickness (i.e. invasion depth of the primary melanoma) was associated with progressive suppression of skin-derived migratory CD1a+ DC-subsets. In contrast, LN-resident DC-subsets and T cells were only affected once metastasis to the SLN had occurred. In stage III patients, increased CD4:CD8 ratios in concert with the accumulation of Tregs resulted in decreased CD8:Treg ratios. On follow-up, lower frequencies of migratory DC subsets proved related to local melanoma recurrence, whereas reduced maturation of LN-resident DC-subsets was associated with distant recurrence and melanoma-specific survival. In conclusion, melanoma-mediated suppression of migratory DC subsets in the SLN precedes locoregional spread, whereas suppression of LN-resident DC subsets follows regional spread and precedes further melanoma dissemination to distant sites. This study offers a rationale to target migratory as well as LN-resident DC subsets for early immunotherapeutic interventions to prevent melanoma recurrence and spread.