Background: Recurrent gene rearrangements are important drivers of lung cancer growth. While RET fusions are recognized as actionable targets, the clinicopathologic features of these drivers in advanced (stage IIIB/IV) disease and survival in comparison to ALK and ROS1 fusion-positive lung cancers are less well-characterized. Methods: A FISH study using dual-color break-apart probes was performed to screen for RET fusions in patients (pts) with advanced lung ADCs that tested negative for mutations in EGFR, KRAS, NRAS, BRAF, MAP2K1, ERBB2, PIK3CA, or AKT, and fusions of ALK or ROS1. In pts with sufficient tissue, fusion partners were identified (RT-PCR/next-generation sequencing). Pathologic review of available tumor specimens and assessment of radiographic response via RECIST v1.1 were conducted. Overall survival (OS) and progression-free survival (PFS) were determined using Kaplan-Meier estimates. Comparisons to control groups of ALK and ROS1 fusion-positive lung cancers were performed (Mantel-Haenszel/log rank tests). Results: 17% (n=18/104, 95%CI 9-22%) of tumors from screened pts harbored a RET fusion (56% male, median age 61). Majority of pts had no history of chest RT [89%, n=16] and were never smokers [72% (n=13) <1, 22% (n=4) 1-15, and 6% (n=1) >15 pack-years]. In 8 pts with sufficient tissue, known upstream partners were identified in 7 pts (NCOA4, TRIM33, 6 KIF5B). An upstream partner not previously described in lung cancers (CLIP1) was found. Morphology in surgical specimens (n=8) was as follows: 63% (n=5) predominantly solid, 25% (n=2) predominantly cribriform, 13% (n=1) predominantly papillary. OS of RET (n=18) vs ALK (n=45; HR 0.84, 95%CI 0.34-2.08, p=0.71) and ROS1 (n=10; HR 1.59, 95%CI 0.34-7.31, p=0.55) fusion-positive lung cancers was similar. In patients who received first-line chemotherapy, PFS of RET (n=12) vs ALK (n=22; HR 0.53, 95%CI 0.25-1.13, p=0.10) and ROS1 (n=8; HR 1.19, 95%CI 0.34-4.17, p-0.78) fusion-positive lung cancers was similar. Conclusions: Advanced RET fusion-positive lung cancers represent a distinct group of tumors with clinical outcomes comparable to ALK and ROS1 fusion-positive lung cancers.