Objectives: Elective neck dissection is frequently performed during surgery in head and neck cancer patients. The sentinel lymph node (SLN) procedure can prevent the morbidity of a neck dissection and improve lymph node staging by fine pathology. Near-infrared (NIR) fluorescence imaging is a promising technique to identify the sentinel lymph node (SLN) intraoperatively. This feasibility study explored the use of indocyanine green adsorbed to human serum albumin (ICG:HSA) for SLN mapping in head and neck cancer patients. Materials and methods: A total of 10 consecutive patients with oral cavity or oropharyngeal cancer and a clinical N0 neck were included. After exposure of the neck, 1.6 mL of ICG: HSA (500 mu M) was injected at four quadrants around the tumor. During the neck dissection, levels I-IV were measured for fluorescence using the Mini-FLARE imaging system. Results: In all 10 patients, NIR fluorescence imaging enabled visualization of one or more SLNs. A total of 17 SLNs were identified. The mean contrast between the fluorescent signal of the lymph nodes and of the surrounding tissue was 8.7 +/- 6.4. In 3 patients, of which 1 was false-negative, lymph node metastases were found. After administration of ICG: HSA, the average number of fluorescent lymph nodes significantly increased over time (P < 0.001). Conclusion: This study demonstrated feasibility to detect draining lymph nodes in head and neck cancer patients using NIR fluorescence imaging. However, the fluorescent tracer quickly migrated beyond the SLN to higher tier nodes. (C) 2012 Elsevier Ltd. All rights reserved.