Background: Aberrant alternative splicing (AS) events have been implicated in the initiation and progression of various cancers; however, the detailed nature of their role in RCC is yet to be fully elucidated. Our study aims to characterize AS events in RCC tumors using a novel AS pipeline (Bisbee). Methods: We retrospectively identified patients (pts) with RCC who had tumor-normal whole exome sequencing and tumor whole transcriptome sequencing (GEMExtra, Ashion Analytics) performed as part of their routine clinical care. AS events from RNA sequencing data were identified and further characterized as (1) alternative splice 3’ site (A3), (2) alternative splice 5’ site (A5), (3) exon skipping (ES), (4) intron retention (IR), and (5) mutually exclusive exons splice events (MUT). The Bisbee outlier analysis was performed against normal kidney tissues from the GTEx tissue library to further identify tumor-associated splice events. Outlier splice events were categorized as either non-coding/protein loss/silent, isoform switch, novel, or unknown. Results: Overall, 147 RCC pts (77% male) with RNA sequencing data were included in this analysis. Median age at diagnosis was 60 (range 31-94) and 97% of pts had metastatic RCC. The distribution of histology was 85% clear cell RCC followed by 11% papillary RCC. The AS analysis identified 25,928 outlier splice events. Approximately 60% of these were predicted to be protein-coding events, with the majority arising from IR and ES. These were followed by A3, A5, and MUT, in descending order of frequency. We also examined tumor-associated novel outlier events where 70% of analyzed RCC tumor samples noted 34 tumor-associated novel events were present, shared in most of the cohort and found an enrichment for IR events leading to frame disruptions. Data of splice variants will be presented at the meeting. Conclusions: In depth examination of this large cohort suggests that IR resulting from AS events occur frequently within RCC. Further efforts to investigate the association of AS events and clinical outcomes are underway.