Adenoid cystic carcinoma of the salivary glands is characterized by a poor response to chemotherapy. Most cases of adenoid cystic carcinoma express the c-kit protein. Imatinib mesylate (Gleevec) inhibits several protein-tyrosine kinases, including c-kit. We therefore hypothesized that Imatinib may be an effective drug in patients with locally advanced or metastatic adenoid cystic carcinoma and conducted a phase 2 trial in order to study this. Patients with locally advanced or metastatic adenoid cystic carcinoma and c-kit positive tumours were eligible. Fourteen patients were screened and 10 patients (71%) with c-kit positive tumours entered the study. Treatment was begun at a dose of Imatinib of 400mg/day. Dose escalation was allowed in the absence of toxicity. The dose was increased to 600mg/d in three patients and 800mg/d in one patient. Three patients required dose reduction to 300mg/d, due to grade 3 toxicity. No grade 4 toxicity was seen. No objective responses were seen. Two patients (20%) exhibited stable disease for 11 and 14 months, respectively. All other patients stopped treatment after 2-14 (median 6) months due to progressive disease. Imatinib has no major effect on advanced adenoid cystic carcinoma of the head and neck.