Objectives: Laser therapy is becoming a more precise, minimally invasive alternative for tumor ablation, Recent reports confirm successful palliation of pain and functional disabilities in patients with advanced deep carcinoma of the head and neck using interstitial laser phototherapy (ILT), Study Design, Patients, and Methods: The current study describes an ongoing Phase II trial of neodymium/yttrium- aluminum-garnet (Nd:YAG) laser therapy for palliation of advanced head and neck cancer. A total of 40 advanced cancer patients have been entered into this protocol (25 men and 15 women). Results: Nineteen of these patients had no evidence of recurrence after ILT with an average follow-up of 11 months (range, 2 to 24 mo). Currently, 19 of these patients are alive, 14 with tumor remission and six with persistent disease. A total of 79 tumor sites received ILT with 43 (54.5%) completely ablated, Stratified by tumor site, ILT led to a complete response in 21 of 24 in the oral cavity, eight of 28 neck tumors, four of 10 in skin, and 10 of 17 in other sites. The procedure was well tolerated in most cases and was repeated at intervals in patients with residual disease or recurrences for a total of 118 laser treatments (average, 2.95 treatments per patient). Conclusions: The results suggest that ILT can be performed safely and repeated as needed, and may be less costly than conventional surgery for head and neck cancer. However, additional follow-up is needed to obtain convincing evidence of long-term therapeutic benefits.