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Background  The number of predictive biomarkers that will be necessary to assess in clinical practice will increase with the availability of drugs that target specific molecular alterations. Therefore, diagnostic laboratories are confronted with new challenges: costs, turn-around-time and the amount of material required for testing will increase with the number of tests performed on a sample. Our consortium of European clinical research laboratories set out to test if semi-conductor sequencing provides a solution for these challenges.    Methods  We designed a multiplex PCR targeting 87 hotspot regions in 22 genes that are of clinical interest for lung and/or colorectal cancer. The gene-panel was tested by 7 different labs in their own clinical setting using ion-semiconductor sequencing.    Results  We analyzed 155 samples containing 112 previously identified mutations in the  KRAS ,  EGFR  en  BRAF  genes. Only 1 sample failed analysis due to poor quality of the DNA. All other samples were correctly genotyped for the known mutations, even as low as 2%, but also revealed other mutations. Optimization of the primers used in the multiplex PCR resulted in a uniform coverage distribution over the amplicons that allows for efficient pooling of samples in a sequencing run.    Conclusions  We show that a semi-conductor based sequencing approach to stratify colon and lung cancer patients is feasible in a clinical setting.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-015-1015-5) contains supplementary material, which is available to authorized users.

Development of a semi-conductor sequencing-based panel for genotyping of colon and lung cancer by the Onconetwork consortium