In this feasibility study we applied next generation sequencing (NGS) based whole exome sequencing (WES) of tumor tissue and peripheral blood of patients with metastatic breast (MBC, n = 44) or advanced gynecological cancer (AGC, n = 8). The purpose was to select targeted therapies according to "ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)". Data interpretation was further supported by a browserbased Treatment Decision Support platform (MH Guide → , Molecular Health, Heidelberg, Germany).We identi ed 25 genomic alterations (GAs) with ESCAT LoE I or II in 18/32 MBC patients, which were available for evaluation: three copy number gains in ERBB2, two gBRCA1, two gBRCA2, six PIK3CA, one ESR1, three PTEN, one AKT1 and two ERBB2 mutations. In addition, ve samples displayed MSI-H. In AGC we found one somatic BRCA1 mutation and one patient with a MSI-H endometrial cancer out of seven evaluable patients.Resulting treatment options were discussed in the molecular tumor board and could be recommended in a small but relevant proportion of patients with MBC (7/18). However, WES still is a technical challenge with sometimes long processing times and high costs. With a customized panel (38 genes), we want to shorten time for analyses and optimize selection of targeted therapies.