Background: A recent twin study found melanoma to be the most heritable cancer with high twin-twin concordance (Mucci et al., JAMA 2016). Of melanoma patients presenting to oncology, 29% had a family history of ≥3 cancers, 59% had cancer in a 1^st degree relative, and 17% had a family history of melanoma (Sussman et al., SMR 2017). The clinical utility of multiplex germline testing in the oncologic melanoma population has not yet been established. Methods: Consecutive patients who met criteria were offered germline testing with a multiplex panel (Invitae, San Francisco, CA) comprised of 12 genes related to melanoma and 69 additional cancer-related genes not known to be related to melanoma. Eligibility criteria included ≥ 2 melanomas in an individual or family; melanoma and other cancer(s) in an individual; melanoma and at least 2 other cancers in 1^st- or 2^nd-degree relatives, including a 1^st-degree relative; age ≤35 at diagnosis; and limited family structure. Results: Of 81 patients with completed testing, 15 (18.5%) had a pathogenic/likely pathogenic mutation. 8 (53%) mutations were in genes previously associated with melanoma (CDKN2A, BRCA1/2, BAP1, TP53), and 7 (47%) were in genes from an extended pan-cancer panel (CHEK2,PMS2,RAD51C, BLM, MUTYH). Study eligibility met by mutation-positive individuals included 9 (60%) with a personal history of multiple cancers, 6 (40%) with multiple relatives with cancer, 4 (33%) with family history of ≥2 melanomas, 3 (20%) age ≤35 years, 2 (13%) with personal history of ≥3 melanomas, and 1 (7%) with limited family history. Melanoma subtypes of mutation-positive probands included 12 cutaneous, 1 mucosal, and 2 uveal. Other cancers observed in probands/families: bladder, brain, renal, pancreatic, carcinoid, thyroid, lymphoma, colon, breast, and ovarian cancers. Conclusions: Multiplex germline testing in a melanoma cohort selected by family or personal history of multiple cancers resulted in an 18.5% mutation-positive rate, nearly half identified in genes not previously associated with melanoma. Patients with melanoma, particularly with a personal or family history of other cancers, may benefit from germline testing. More data will be required to further refine testing guidelines for melanoma.