Existing studies have reported conflicting associations between primary tumor location (PTL) and mortality in cutaneous malignant melanoma (CMM) patients.

To evaluate the association of PTL with mortality among CMM patients.

This was a multicenter, retrospective study from Surveillance, Epidemiology, and End Results (SEER) program from 2000-2021. Patients with histologically confirmed primary CMM were included.

Among 162,871 patients (56.4% male; 74.0% >=50 years), 23.0% died during median 6.3-year follow-up (interquartile range, 2.7-10.9). The multivariate Cox model showed that head and neck [HN] site was significantly associated with increased risk of all-cause (adjusted hazard ratio [aHR]: 1.08, 95% confidence interval [CI] 1.05-1.12) and cancer-specific mortality (aHR: 1.05, 95%CI, 1.02-1.09), but sites in upper limb/shoulder [ULS] and lower limb/hip [LLH] were significantly associated with decreased risk of all-cause (ULS: aHR: 0.91, 95%CI, 0.89-0.94; LLH: aHR: 0.89, 95%CI, 0.86-0.92) and cancer-specific mortality (ULS: aHR: 0.79, 95%CI, 0.75-0.84; LLH: aHR: 0.96, 95%CI, 0.92-1.00), compared with trunk. The associations were consistent in various subgroups and sensitivity analyses.

Retrospective design may introduce selection bias.

HN site has higher risk of all-cause and cancer-specific mortality compared to the trunk site, whereas this effect is reversed at the sites of LLH and ULS.