Abstract Melanoma survival appears to be improving; however, between 13-68% of individuals with melanoma diagnosed with Stages II-III ultimately die from their melanoma. Factors influencing melanoma survival include sex, age, clinical stage, lymph node involvement and several primary tumor characteristics, such as Breslow thickness, presence of infiltrating lymphocytes (TILs), mitotic rate and ulceration. Identification of genes whose expression in primary tumors is associated with these key tumor/patient characteristics can shed light on molecular mechanisms of melanoma survival. Here we show results from a gene expression analysis of 32 formalin-fixed, paraffin embedded (FFPE) primary melanomas with extensive clinical annotation. We extracted RNA, and measured the expression of 760 genes selected based on published evidence of association with melanoma initiation or outcome using NanoString. The Cancer Genome Atlas (TCGA) data on primary melanomas was used for validation of nominally significant associations. We identified 5 genes that were significantly associated with the presence of TILs in the combined analysis of both datasets after adjustment for multiple testing using the Benjamini-Hochberg false discovery rate method: IL1R2, PPL, PLA2G3, RASAL1, and SGK2. We also identified two genes significantly associated with lymph node status (PIK3CG and IL2RA), and two genes significantly associated with sex (KDM5C and KDM6A). We found that LEF1 was significantly associated with Breslow thickness and CCNA2 with mitosis. These results demonstrate that genetic expression in primary tumors is associated with clinically meaningful characteristics of cutaneous melanoma. Citation Format: Marianne Berwick, Ivan P. Gorlov, Irene Orlow, Carol Ringelberg, Marc Ernstoff, Joel Parker, Meg Gerstenblith, Cheryl Thompson, Eva Hernando, Klaus Busam, Cecilia Lezcano, Sergio Corrales, Siok Leong, Nancy E. Thomas, Christopher I. Amos. Expression levels of genes in primary melanoma associated with clinically meaningful characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3682.