For cancer treatment, diagnostics concerning tumor type and determination of molecular markers in short TAT is critical. The fully automated, real-time PCR-based molecular diagnostic Idylla assays are well established in many laboratories for qualitative detection, short TAT and routine screening of clinically relevant oncogenic mutations. According to the manufacturer, all IVD assays are recommended for use only with FFPE tissue samples of 5–10 µM dissections with at least 10% tumor content. In this study, we tested the performance and accuracy of the IVD assays along with the gene fusion assay (RUO) with different tissue/source materials like isolated DNA/RNA, cryomaterial, etc. The study also included testing archival FFPE tissue sections dating back from 20 years and a performance check for different pan-cancer samples individually. All the assays tested with FFPE sections and gDNA/RNA input showed above 96% accuracy and sensitivity, individually with 100% specificity. The Idylla assays also performed exceptionally well on the archival FFPE tissues, and the use of assays for other solid tumors was also remarkable. The performance test and accuracy of Idylla assays showed high efficiency with certain limitations. For the use of Idylla assays, both qualitative and quantitative applicability of different tumor source materials could produce efficient results in different diagnostic settings within a short TAT.