Background. No systemic therapy regimen has been recognized as effective for metastatic mucosal melanoma of the head and neck. We retrospectively analyzed the effectiveness of biochemotherapy in patients with advanced head and neck mucosal melanoma. Methods. We evaluated the medical records of 15 patients at our institution who had received various biochemotherapy regimens for advanced head and neck mucosal melanoma. Results. After a median follow‐up duration of 13 months, 3 patients (20%) had partial response, and 4 patients (27%) had complete response. The median time to disease progression for all 15 patients was 10 months. The median overall survival duration for all patients was 22 months. Conclusions. Although this was a small study, our results, especially the high complete response and overall response rates, indicate that biochemotherapy for advanced head and neck mucosal melanoma should be considered as a systemic treatment option for patients with this aggressive malignancy. © 2008 Wiley Periodicals, Inc. Head Neck, 2008