Colorectal cancer ist the 2nd most leading cancer among men and women in germany. Screening colonoscopy is provided for all people over 55 years in germany to detect and remove precancerous lesions (polyps) and thereby prevent the occurence of colorectal cancers. According to the result of screening colonoscopy and histopathological examination of the removed polyps the next examination will be planned. But so called interval carcinomas were observed with increasing incidence. Thus, further tools and mechanisms, beyond but in addition to endoscopy and histopathology, are strongly required to reduce such interval carcinomas and get a better and deeper inside into molecular alterations which occurs in premalignant lesions in the colon and describe risk populations which might benefit from shorter surveillance strategies by colonoscopy. Therefore we will enroll 100 patients, which underwent screening colonoscopy with polyp ectomy. Each polyp, provided for endoscopical removal, well be biopsied and stored separately. In each case, diagnosis is ensured. Per patient a maximum of 6 biopsies (from 6 different polyps) is intended. All biopsies were stored and processed without formalin in special boxes (PaxGene by Qiagen®). After microdissection of polyp tissue and isolation of DNA targeted next generation sequencing of 38 genes (ACVR1B, DCC, MIER3, SLC9A9, AKT1, DMD, MLH1, SMAD2, APC, EP300, MSH2, SMAD4, ATM, ERBB2, MSH3, TCERG1, ATP6V0D2, FBXW7, MSH6, TCF7L2, BAX, FZD3, MYO1B, TGFBR2, BRAF, GPC6, NRAS, TP53, CASP8, KRAS, PIK3CA, WBSCR17, CDC27, MAP2K4, PIK3R1, CTNNB1, MAP7, PTPN12) followed by bioinformatics and systems biology analyses. The sequencing results were correlated to the endoscopical and histopathological findings. In parallel we are collecting EDTA-blood samples for analysis of circulating cell-free DNA (cfDNA). NGS targeted sequencing of these 38 genes should also be performed on cfDNA level to investigate the potential of liquid biopsies in premalignant colorectal lesions.