For the differential diagnosis of head and neck mass lesions, the age and presenting locations should be the primary considerations. The characteristic patterns of age- and site-predilection allow a diagnostic work-up and treatment plans for the patients with head and neck mass lesions. In children and young adults, the underlying causes are; inflammatory, congenital and developmental, and neoplastic masses in decreasing frequency. By contrast, neoplastic diseases are most frequent in the elderly. Because of the characteristic lymphatic spread patterns of head and neck diseases, the location of the mass in the cervical lymphatic nodal chain may be the key for the identification and differential diagnosis of the primary disease site. Besides, the evaluation of specific historical and physical findings is mandatory for the accurate diagnosis. When the signs of inflammation are associated, conservative treatment and observation is first considered. On the other hand, for persistent or progressively enlarging masses and those with suspicious findings of malignancy, surgical intervention should be considered.