Background: Studies in certain cancer types have indicated that radiation therapy prior to the use of CBI provides a survival benefit. This benefit has not been clearly defined for patients with metastatic melanoma. Additionally, the neutrophil-to-lymphocyte ratio (NLR) may be a potential biomarker. Methods: This retrospective study was performed in patients diagnosed with melanoma between January 2007 and August 2016 who received CBI with or without previous radiation treatment at Intermountain Healthcare (Utah, USA). Cases were identified from electronic medical records and data was manually extracted through August of 2017. The neutrophil-to-lymphocyte ratio (NLR) was calculated from the absolute neutrophil and lymphocyte counts of a complete blood cell count with differentials performed as a routine standard of care procedure in melanoma patients prior to therapy initiation. Overall survival was defined as the length of time (d) from start of CBI to death as of August, 2017. Results: Forty-six melanoma patients were initially identified. Of these, thirteen patients were excluded due to lack of follow-up data (n = 9), radiation performed after CBI (n = 3), or concurrent radiation and CBI (n = 1). The final analysis consisted of 33 subjects separated below (NLR < 3.12, n = 16) and above (NLR ≥ 3.12, n = 17) the NLR median. Age, height, body mass, and body mass index were not significantly different between groups (p-range: 0.11-0.60). Results from the Kaplan-Meier curve indicate that a NLR above the median associates with lower overall survival (Mantel, p = 0.04) in melanoma patients receiving CBI with or without previous radiation treatment. In a separate analysis of this cohort, overall survival was not significantly influenced by radiation therapy prior to CBI. Conclusions: Although prior radiation therapy offered no survival advantage for patients receiving CBI, NLR less than 3.12 was associated with an increase in overall survival. Further studies are need to explore NLR as a biomarker.