Background Most head and neck melanomas occur on the face, with the cheek being the most frequently affected site. So far, small numbers of researches on cheek melanomas have yielded insufficient and controversial results. In this trial, we aimed to define the histopathological and clinical features specific to cheek melanomas and to compare them with other head and neck melanomas by using a large group of patients from a single tertiary center. Patients and Methods A total of 98 cheek melanomas and 183 other (noncheek) head and neck melanoma cases were analyzed retrospectively. Results The median age was 62 years and malar/zygomatic was the mostly affected site (78.6%). The cheek melanomas developed more frequently in females (61.2%) and most of them were associated with lentigo maligna histopathological subtype (49.2%) and early-stage disease (stage 0-II) (77.6%). The cheek melanomas were found more significantly associated with older patients (P = 0.05), females (P = 0.0001), lentigo maligna subtype (P = 0.0001), lower vertical growth phase (P = 0.03), and early-stage of disease (P = 0.0001) compared with other lesions that developed other sites. Furthermore, they were associated with lower relapse rates (18.6% vs 39.5%, P = 0.0001) and the 5-year recurrence-free survival rate of cheek melanomas was 80% (P = 0.002). Moreover, the 5-year overall survival rate of cheek melanomas was 62%, and they were found to be associated with a favorable overall survival (P = 0.004). Conclusions Cheek melanomas are associated with lower relapse rates and favorable outcomes compared with other (noncheek) head and neck melanomas.