Background <p>Cutaneous and mucosal melanoma are biologically and clinically distinct malignancies whose epidemiology varies markedly across populations and skin phototypes. In Arab and other Eastern Mediterranean populations, melanoma is comparatively uncommon but is frequently diagnosed at an advanced stage and shows a relatively high proportion of acral and mucosal subtypes. Data describing melanoma in the Palestinian population are scarce. We characterised the clinicopathological profile of cutaneous and mucosal melanoma diagnosed at a large Palestinian diagnostic pathology service and placed the findings in a comparative regional context.</p> Methods <p>We performed a retrospective review of all histopathologically confirmed cases of cutaneous and mucosal melanoma reported at Medicare Diagnostic Laboratories, West Bank, Palestine, between May 2008 and May 2026. Demographic variables (age, sex), anatomical site, melanoma subtype, depth of invasion (Clark level), and, where recorded, Breslow thickness and American Joint Committee on Cancer (AJCC) stage were abstracted from pathology records. Diagnoses were confirmed on haematoxylin-eosin sections supported by immunohistochemistry (S100, SOX10, HMB-45, Melan-A). Repeat specimens were consolidated to the patient level, and findings were compared with published series from neighbouring countries.</p> Results <p>Fifty-seven patients with primary melanoma were identified, comprising 47 cutaneous (82.5%) and 10 mucosal (17.5%) tumours. The mean age at diagnosis was 59.5 +/- 17.0 years (range 10–87), and there was a slight female predominance (30 women, 52.6%; male-to-female ratio 0.90:1). Acral sites (sole, heel, plantar, and subungual regions) accounted for 15 of 47 cutaneous melanomas (31.9%), the most common single location, followed by the head and neck (14, 29.8%). Among mucosal tumours, the anorectum was the predominant site (6 of 10, 60%). A histological subtype was explicitly recorded in only 19 of 57 cases; within this limited subset the nodular pattern predominated (18 of 19), although the large proportion of cases without a stated subtype precludes firm conclusions about the true distribution of melanoma subtypes in this cohort. The Clark level was documented in 27 patients, of whom 26 (96.3%) had level IV-V (deep) invasion. A further 17 patients presented with metastatic melanoma deposits without a primary tumour in the archive.</p> <p>Melanoma in this Palestinian cohort was characterised by a slight female predominance, a high proportion of acral (31.9% of cutaneous) and mucosal (17.5% of all primary) tumours, a predominantly nodular phenotype among the subset of cases with a recorded subtype, and deep invasion at diagnosis. This profile mirrors patterns reported in neighbouring Arab and Eastern Mediterranean populations and contrasts with more lightly pigmented (Fitzpatrick I–II) Western populations. The findings underline the need for improved melanoma awareness, routine examination of acral and mucosal sites, and strengthened cancer registration in Palestine.</p>