Purpose To evaluate the utility of amide proton transfer (APT) imaging in the characterization of head and neck tumors. Materials and Methods This retrospective study of APT imaging included 117 patients with 70 nasopharyngeal undifferentiated carcinomas (NUCs), 26 squamous cell carcinomas (SCCs), eight non-Hodgkin lymphomas (NHLs), and 13 benign salivary gland tumors (BSGTs). Normal tissues were examined in 25 patients. The APT means of malignant tumors, normal tissues, and benign tumors were calculated and compared with the Student t test and analysis of variance. The added value of the mean APT to the mean apparent diffusion coefficient (ADC) for differentiating malignant and benign tumors was evaluated by using receiver operating characteristic analysis and integrated discrimination index. Results The mean APT of malignant tumors (2.40% ± 0.97 standard deviation) was significantly higher than that of brain tissue (1.13% ± 0.43), muscle tissue (0.23% ± 0.73), and benign tumors (1.32% ± 1.20) (P < .001). There were no differences between malignant groups (NUC, 2.37% ± 0.90; SCC, 2.41% ± 1.16; NHL, 2.65% ± 0.89; P = .45 to P = .86). The mean ADC of malignant tumors (0.85 ± 0.17 × 10 mm /sec) was significantly lower than that of benign tumors (1.46 ± 0.47 × 10 mm /sec) (P = .001). Adding APT to ADC increased the area under the curve from 0.87 to 0.96, with an integrated discrimination index of 7.6% (P = .13). Conclusion These preliminary data demonstrate differences in amide proton transfer (APT) mean of malignant tumors, normal tissues, and benign tumors, although APT mean could not be used to differentiate between malignant tumor groups. APT imaging has the potential to be of added value to apparent diffusion coefficient in differentiating malignant from benign tumors.