The sentinel lymph node (SLN) is regarded as the first tumor-draining lymph node, which may be the initial site activated by tumor antigens. To clarify the immunological functions of SLNs, a total of 89 tumor-free regional lymph nodes (41 SLNs and 48 non-SLNs) were obtained from 12 patients with oral cavity cancer, and infiltration of both DCs and NK cells was determined by immunohistochemistry. S-100+ and CD1a+ DCs infiltrated significantly into SLNs compared to non-SLNs. Analysis in each of the pN0 and pN+ patients showed that all the DC markers in pN0 patients and only S-100+ in pN+ patients were significantly more abundant in SLNs. Moreover, infiltration of CD83+ DCs was less in pN+ patients than in pN0 patients. These results suggest that more significant immune responses against cancer occur in SLNs than in non-SLNs. However the progression of disease including nodal disease may cause systemic immunosuppression.