Background: Most of targetable gene alterations are found only in 1-5% of non-small cell lung cancer (NSCLC) cases. Large scale screening systems for these rare populations are necessary for the development of molecular targeted therapies. Thus, a nationwide lung cancer genomic screening project in Japan (LC-SCRUM-Japan) has been operated since February 2013. Methods: Non-squamous NSCLCs without EGFR mutations were eligible for inclusion in this study. The tumors were analyzed for ALK/RET/ROS1 fusions using RT-PCR, and detected fusions were confirmed by FISH. Since March 2015, this nationwide project has been amended to an academic-industrial collaboration project with 14 pharmaceutical companies, and the samples were further subjected to a next-generation sequencing (NGS) system, Oncomine Comprehensive Assay, enabling the simultaneous analysis of 143 cancer-related genes. Results: As of December 31, 2015, 195 institutions across Japan were participating and 2161 patients had been enrolled. Among 1988 available samples, including 497 for the NGS analysis, ALK/RET/ROS1 fusions were detected in 37 (2%)/51 (3%)/86 (4%), respectively. The NGS analysis also showed that 269 cases (54%) had targetable gene alterations, including 82 KRAS mutations (17%), 36 ERBB2 mutations (7%), 28 BRAF mutations (6%), 22 PIK3CA mutations (4%), 6 NRAS mutations (1%), 6 MAP2K1 mutations (1%) and 2 FGFR2 fusions (0.4%). MET/ERBB2/FGFR1 amplifications were also detected by the NGS in 13 (3%)/11 (2%)/3 (1%) cases, respectively. Through this screening, the preplanned numbers of patient with RET and ROS1 fusions (n = 19 and 26, respectively) were successfully enrolled in clinical trials of vandetanib (LURET study in Japan) and of crizotinib (OO12-01 study in East Asia), respectively. Three patients with ERBB2 alterations and 2 with MET amplifications were also enrolled in genotype-matched ongoing trials. Conclusions: This nationwide screening system enables efficiently and successfully detecting various targetable gene alterations in NSCLC, thereby contributing to promote cancer precision medicine through the development of targeted therapies.