Background: Somatic mutations in the promoter of the telomerase reverse transcriptase gene (TERT) appear to confer a worse prognosis in several cancers, an effect which may be modulated by inheritance of nearby germline polymorphism. Methods: We analyzed primary tumors from a cohort of prospectively accrued melanoma patients for sequence variants in the TERT promoter (somatic and germline). We tested the associations between these variants and several other variables including BRAF and NRAS mutations, and clinicopathologic factors including survival outcomes using Chi-Square test and log rank test for Kaplan Meier analysis. We used SNaPshot assays and Sanger sequencing to detect BRAF V600; NRAS Q61; and TERT -124 (C > T) and -146 (C > T) mutations, and the rs2853669 germline polymorphism. Results: Among 367 patients 212 (58%) were male; 188 (51%) were over 60 years old; and 227 (62%), 96 (26%), and 44 (12%) had stages I, II, and III disease respectively. Fifty patients recurred; median follow up was 3.6 years. We found TERT -124 (C > T) mutations in 77/367 (21%) patients and -146 (C > T) mutations in 113/367 (31%) patients. TERT promoter mutations were significantly associated with age > 60 years (p= 0.022), nodular histotype (p= 0.006), higher stage (p= 0.009), thicker tumors (p= 0.021), and ulceration (p= 0.013). TERT promoter mutations were significantly associated with shorter recurrence-free survival (RFS) (p= 0.010). While neither BRAF nor NRAS mutations alone were significantly associated with survival outcomes, they were associated with shorter survivals when co-occurring with TERT mutations (p= 0.015). Patients with the TERT rs2853669 variant whose tumors had the -124 promoter mutation had shorter RFS than those with the -124 mutation alone (p= 0.029). Conclusions: TERT promoter mutations have a significantly deleterious impact on RFS in patients with primary melanoma regardless of mutations in BRAF and NRAS. Importantly, the presence of the inherited rs2853669 variant may further accentuate the impact of TERT mutations on survival. TERT sequence variants may be useful biomarkers to identify early/intermediate stage patients at high risk of recurrence.