Successful identification and targeting of oncogenic gene fusion is a major breakthrough in cancer treatment. Here, we investigate the therapeutic implications and feasibility of using a targeted RNA sequencing panel to identify fusion genes in gastrointestinal and rare cancers. From February through December 2017, patients with gastrointestinal, hepatobiliary, gynecologic, sarcoma, or rare cancers were recruited for a clinical sequencing project at Samsung Medical Center (NCT #02593578). The median age of the patients was 58 years (range, 31–81 years), and the male-to-female ratio was 1.3 : 1. A total of 118 patients passed the quality control process for a next-generation sequencing- (NGS-) based targeted sequencing assay. The NGS-based targeted sequencing assay was performed to detect gene fusions in 36–53 cancer-implicated genes. The following cancer types were included in this study: 28 colorectal cancers, 27 biliary tract cancers, 25 gastric cancers, 18 soft tissue sarcomas, 9 pancreatic cancers, 6 ovarian cancers, and 9 other rare cancers. Strong fusion was detected in 25 samples (21.2%). We found that 5.9% (7/118) of patients had known targetable fusion genes involving NTRK1 (n=3), FGFR (n=3), and RET (n=1), and 10.2% (12/118) of patients had potentially targetable fusion genes involving RAF1 (n=4), BRAF (n=2), ALK (n=2), ROS1 (n=1), EGFR (n=1), and CLDN18 (n=2). Thus, we successfully identified a substantial proportion of patients harboring fusion genes by RNA panel sequencing of gastrointestinal/rare cancers. Targetable and potentially targetable involved fusion genes were NTRK1, RET, FGFR3, FGFR2, BRAF, RAF1, ALK, ROS1, and CLDN18. Detection of fusion genes by RNA panel sequencing may be beneficial in refractory patients with gastrointestinal/rare cancers.