The knowledge of molecular alterations involved in colon carcinoma (CRC) and non-small-cell lung carcinoma (NSCLC) has significantly increased in the past few years. Molecular subgroups of tumors carrying mutations in druggable genes have been identified in CRC and NSCLC. In this respect, the availability of approaches that are compatible with small amounts of input DNA from FFPE tissue and that allow a rapid screening of a large number of somatic mutations is definitely needed. Ion AmpliSeq technology introduces a groundbreaking workflow enabling the rapid sequencing of hundreds of mutations with low allele frequency using as little as 10ng of DNA per reaction. The OncoNetwork Consortium is a European collaborative effort of 8 Cancer Translational Research Institutions to evaluate a custom panel targeting hotspots mutations in 22 genes implicated in CRC and NSCLC. In particular, 7 labs will test the gene panel in 3 phases using 180 retrospective FFPE samples previously tested with orthogonal technologies, and 1 lab will perform confirmatory testing on novel SNPs.