Background: We conduct the nationwide cancer genome screening project in Japan from February 2014. Since February 2015, we introduced Next Generation Sequencing method to detect cancer genome alterations in advanced colorectal cancer (aCRC), called as SCRUM-Japan GI-SCREEN 2013-01-CRC. The objective is to evaluate the frequency of cancer genome alterations in aCRC and to identify patients who are candidate for clinical trial for corresponding targeting agents. Methods: This study is ongoing with the participation of 20 major cancer centers. Patients with aCRC who plan to or receive systemic chemotherapy were eligible. Twenty ng of DNA and 10 ng of RNA were extracted from formalin-fixed paraffin embedded (FFPE) tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to whether genetic driver of cancer, including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. Results: As of October 31^st in 2015, a total of 393 aCRC patients were enrolled and 360 samples were available. Out of 360 samples, 345 samples were analyzed and 15 samples are currently under analysis. The sequence with the OCP was successfully performed in 257 tumors (74.5%). The most frequently detected mutations were TP53 (66.9%), APC (56.4%), KRAS (38.9%), PIK3CA (12.1%), and BRAF (10.9%), and CNVs were ERBB2 (3.5%), FLT3 (2.3%), MYC (1.9%), and FGFR1 (1.6%). No gene fusion was detected so far. Patients with BRAF, PIK3CA or FGFR1 mutation were enrolled in early clinical trials. We plan to conduct the investigator initiated studies targeting aCRC patients with ERBB2 amplification and those with BRAF non-V600E mutations. Conclusions: This nationwide screening system is efficient to detect rare mutations in aCRC. This novel knowledge provides an intriguing background to investigate new target approaches in these patients and represents a progress toward more precision medicine. Clinical trial information: UMIN000016343.