The most powerful prognostic factor in patients with oral cancer is the presence of lymph node metastases. The management of the neck at diagnosis in the absence of adenopathy is still controversial, but sentinel lymph node biopsy (SLB) may help resolve this issue. At the National Cancer Institute in Naples, we performed SLB in 41 patients with T1 to T2 oral cancer. All patients underwent lymphoscintigraphy. Intraoperative blue dye and gamma probe examination identified a sentinel node (SN) in 39 patients. Four patients (10%) had double drainage, and 7 (18%) had drainage beyond the expected anatomical site. Complete concordance between the pathology of the SN and nodes obtained from radical dissection confirmed SLB as a reliable staging procedure. Since January 2001, seven patients with T1 to T2 oral cancers have been staged with SLB only; modified radical neck dissection was carried out only in cases with a positive SN. The rate of SN identification was 100%, and all five cases with negative SNs were free of disease after a median follow-up of 10 months. Lymphoscintigraphy plus SLB seems to be a good staging system for guiding neck management in patients with oral cancer. A larger number of patients and a longer follow-up in a randomized trial will confirm the potential staging value of this procedure and determine which patients might benefit from a conservative approach that avoids radical neck dissection.